Final - Carbohydrates, Lipids, Nucleic Acids, Drugs Flashcards

Question

What linkage connects 2 monosaccharides?

Answer 1

Glycosidic linkage (acetal) with at least 1 anomeric C involved

Answer 2

Acidic conditions: hemiacetals and acetals are formed and degraded. Neutral conditions: hemiacetals are unstable, acetals are stable. Basic conditions: hemiacetals are unstable and thus can mutarotate, acetals are stable. If one part of molecule is a hemiacetal, the whole molecule collectively can mutarotate, and be a reducing sugar.

Answer 3

Maltose: alpha(1,4) glycoside linkage - reducing &; mutarotates bc has hemiacetal Cellobiose: beta(1,4) glycoside linkage - reducing &; mutarotates bc has hemiacetal They differ only by the configuration of the anomeric C (aka, cis vs trans)

Answer 4

Lactose: beta(1,4) glycoside linkage btwn D-glucose and D-galactose. These monos only differ by configuration on C4. This bond can be cleaved by lactase enzyme

Answer 5

D-glucose and D-fructose. alpha(1,2) @ glucose beta(2,1) @ fructose If you hydrolyze sucrose, it creates 1:1 mixture of D-gluc and D-fruc ==> "invert sugar". = hydrolyzed product rotates PPL in opposite direction - means that the mixture rotates PPL in different direction (left) from Sucrose (+66) - this mixture is sweeter than sucrose, and has a longer shelf life (aka, it won't crystallize at high concentrations) - sucrose is not a reducing sugar, but when it's hydrolyzed it creates 2 hemiacetals, making it reducing.

Answer 6

- types of polysacc starches that are used as energy storage for plants Amylose: UNbranched chains of D-glucose joined by alpha(1,4) glycosidic bonds, forming a hollow helical structure Amylopectin: Branched polymer of D-glucose with alpha(1,4) linkages in chain, and then branches start with alpha(1,6) bonds.

Answer 7

Energy/carb storage for animals. stored in liver and muscle tissues. Same as amylopectin, except more branches for easier access. Alpha(1,4) and Alpha(1,6)

Answer 8

In plant cell walls. similar to amylose -- unbranched, BUT linear straight chain of BETA(1,4) (thus config of anomeric C is different) Bundles up to form chain bundles (in a crystalline arrangement via H bonding -- because every 2nd unit is rotated for extra bonding)--> microfibrils--> fibrils --> fibres= can be found in cotton, paper, wood. The H bonding makes cellulose very water-insoluble, even though glucose is soluble. Cellulase Enzyme breaks it down into D-glucose EXTRACELLULARLY (outside the microorganism). But only cellulase-producing microorganisms can do this. So humans can't get carbs from plants, but cows can because they're in a symbiotic relationship with these microorganisms.

Answer 9

In laundry detergent. It breaks down cellulose (which is 90% of cotton), so it'll take care of pilling.

Answer 10

Glucose + 2NAD+ +2 ADP + 2 PO43- -----> 2 pyruvates + 2 ATP + 2 NADH Anaerobic process 10 enzymatic steps (1-5 energy consumption, 6-10 energy production)

Answer 11

Steps 1-5: energy consumption. glucose + 2ATP --> 2G3P | Steps 6-10: energy production. 2 G3P ---> 2 pyruvates +4 ATP

Answer 12

Hexokinase converts glucose into G6P by adding a P from ATP (CH2OH to CH2OPO3 2-). USES Mg2+ on ATP O-s!!!

Answer 13

G6P to Fruc6P | Hemiacetal to aldehyde form, then isomerizes it to a ketone via ene-diol rearrangement step.

Answer 14

this enzyme can only act on the BETA anomer of Fruc6P, so if it's in alpha, it'll mutarotate to beta. This is a rate-determining step, and a control point int he pathway. Adds PO32- onto Carbon 1!!

Answer 15

Retro-aldol rxn. In plants and humans, the enzyme uses imine because it's a better electron acceptor than the carbonyl that's there. =NH+---Enzyme !! Creates DHAP and G3P.

Answer 16

DHAP gets isomerized into an aldehyde again via ene-diol mechanism

Answer 17

Oxidative phosphorylation of G3P, with help of NAD+--> NADH. But it's actually performed on the sulfur version of G3P == hemithioacetal (S-Enz at top).

Answer 18

coenzyme NADH is the reducing agent and hydride donor. | NAD+ is the oxidizing agent and hydride acceptor.,

Answer 19

Removes the PO32- on the C1 to create ATP and COO-. | Mg2+ is there as a cofactor.

Answer 20

Moves Phosphate from C3 to C2 by adding a group to C3 and then removing the old one from C3. Enzyme uses a histidine residue Plants take the one at C3 and put it on C2

Answer 21

An H and an OH is taken away to create an enol. Enols are usually very unstable and so are usually found in their keto forms. But this enol has no H on its phosphate so it can't revert to its keto form! The energy in this enol will be used to make ATP.

Answer 22

transfer of phosphate to ADP gives ATP. so now the enol can tautomerize into its stable keto to make pyruvate.

Answer 23

Pyruvate (3 Cs) undergoes OXIDATIVE DECARBOXYLATION which is a successive loss of CO2 using TPP and an oxidation of the C that'll be attached to the CoA by lipoic acid ---> into Acetyl-CoA (2 Cs). Performed by the pyruvate dehydrogenase complex. TPP---> TPP ylide ---> ylide-pyruvate---> - CO2 ---> ENAMINE attacks lipoic acid --> regenerated ylide + CO-oxidized lipoic acid ---> transesterify with CoA-SH to make Acetyl-CoA

Answer 24

Its active part is its thiazolium ring -- weakly acidic and forms a YLIDE. YLIDE = overall neutral compound with pos and neg charges adjacent to each other. (aka, a stabilized carbocation)

Answer 25

FAD is a reducing agent/hydride acceptor that oxidizes lipoic acid. Turning FAD into FADH2

Answer 26

Aminotransferases are enzymes that move amino groups btwn alpha AAs and beta-keto acid carbohydrates and vice versa. Tests for high levels of aminotransferases in blood indicate liver damage.

Answer 27

These rxns btwn AAs and alpha-keto acids require Pyrodoxal phosphate (PLP). PLP is a coenzyme that functions as an amino-group carrier. In the first rxn, the amino group from AA is transferred to PLP, creating an imine of PLP (because its C is involved in C=N). The tautomerization of this imine gives Imine of alpha-keto acid. The hydrolysis of this imine releases pyruvate (alpha keto acid) from the PMP. Rxn 2 is the reverse of rxn 1 except the amino group is moved onto a different alpha-keto acid. PLP is regenerated.

Answer 28

Its long hydrocarbon hydrophobic tail. If fatty acids are ionized (COO-) then they'll be soluble in water.-- but only a tiny amount because the pH drops, stopping further ionization.

Answer 29

Carboxylic acids with long hydrocarbon hydrophobic tails. Highest MP to lowest MP: Saturated>Unsaturated trans>Unsaturated cis. total Cs(usually even):# unsaturations

Answer 30

Some we can synthesize, others we have to get from diet.

Answer 31

Usually monoesters of TWO long-chained fatty acids and alcohols with carbonyl connecting the two.

Answer 32

Glycerol + 3 fatty acids. | Fats when saturated. Oils when polyunsaturated.

Answer 33

Because they're synthesized 2Cs (acetyl units) at a time.

Answer 34

Key step in Chemical Synthesis of Fatty Acids: formation of new C-C bond by joining 2 acetate esters together via a Claisen Condensation (Nu acyl sub rxn using carbanions). condensation==smaller to larger with water as byproduct. The condensation gives a beta-keto ester! Must go through a tetrahedral intermediate too! 1. Condensation (via strong base making enolate,carbanion Nu) 2. Reduction of Carbonyl (NaBH4) 3. Dehydrate (-H2O) 4. Reduction of Alkene (H2/Pd)

Answer 35

In biosynthesis, the Claisen rxn has the SAME 4 steps! But enzymes have to do it instead! Claisen rxns have very small equilibrium constants, so they increase amount of strong base to make more enolate -- but can't do in body because wrong pH, so they use more reactive species. So modified version is to make the rxn more favourable under physiological conditions. Now you don't have to make an alpha-carbanion. Here, condensation gives a beta-keto THIOester.

Answer 36

1: Use thioester instead of oxygen esters. - SR is more electrophilic than OR + SR- is a better LG 2: Use carbanion equivalent (malonyl thioester) - decarboxylation (-CO2) of malonyl thioester gives enolate of acetyl thioester which drives the rxn to completion without need to strong base. malonyl thioester made using Biol (an O carrier) and acetyl thioester(CoA), HCO3-, ATP. Malonyl thioester (3C) adds an acetate unit (2C) to the chain

Answer 37

In one cycle, acetyl-CoA (2C) grows into a 4C chain. Acetyl-CoA/thioester (2C) + malonyl thioester (3C) +-CO2 --> beta-keto thioester (4C)

Answer 38

Well fatty acids need to grow to C16, but we need it to stay in place until it's done so we use an acyl carrier protein (ACP) made from Vitamin B5(=its long arm)+thiol group (SH). ACP is tightly bound to Fatty Acid Synthase complex (FAS) and malonyl so the growing chain doesn't float away.

Answer 39

1. Enzymes with Transacylase activity make a) Acetyl group (E+) binds to FAS. & b) Malonyl-ACP (Nu-) complex binds to ACP-binding site on FAS. 2. An enzyme catalyzes the Claisen-type Condensation rxn with long arm of ACP permitting the movement. 3. The Reduction is enzymatically performed using NADPH --> NADP+ 4. Dehydration by enzyme 5. Reduction of alkene to give a fully reduced tail (NADPH---> NADP+) 6. Growing chain goes to spot of OG Electrophile for next cycle (leaving ACP at its binding site) 7. So E+ is now the growing chain; and a new malonyl thioester comes to bind to ACP. 8. C16 fatty acid released by hydrolysis after 7 CYCLES (7 new C-C bonds)

Answer 40

- growing chain always bound to FAS in/directly - growing chain is always the electrophile, malonyl thioester is the Nu- - growing chain grows on thioester end (SR); because the CH3 end was derived by the first step of acetyl group attaching - the C16 chain's 2 Cs on the end are acetyl-derived, the next 14 are malonyl-derived - could say the C16 fatty acid originates from 8 acetyl units, because the malonyl-derived units themselves are made from acetyl thioester

Answer 41

1. Hydride reagent (NADPH) attacks E+ beta C of the alpha,beta-unsaturated carbonyl [=Conjugate/Michael Addition] giving an enol form 2. This enol form tautomerizes into the alkane product. Hydride reagents don't attack non-polar C=Cs (aka, alkenes can't be reduced by these NABH4, NADH), but since the beta C has some positive characteristic (as seen in resonance structure), and since it's CONJUGATED to the alkene, then it'll happen.

Answer 42

Elongase elongates the C16 fatty acid (by 2C units using malonyl thioester. Desaturase makes monounsaturated fatty acids, producing a CIS alkene using atmospheric oxygen as oxidizing agent! The Delta with the number on top shows which carbon the alkene starts on, counting from the carbonyl carbon.

Answer 43

By hydrolyzing them using lipases (that use Asp-His-Ser)... the hydrolysis products are much better absorbed

Answer 44

Fatty acids---> acetyl-CoA The beta C is oxidized from an alkyl carbon to a ketone. OXIDATION, HYDRATION, OXIDATION, CLEAVAGE 1. FA enzymatically converted to acetyl thioester (O- to SCoA) 2. FAD oxidizes (when in the reverse NADPH was reducing) the saturated tail, creating the alpha,beta-unsaturated thioester (because the C=C starts and ends at alpha and beta Cs) 3. Michael ADDITION of WATER onto the BETA C resaturates it 4. Hydride comes off the beta C and is accepted by NAD+ (aka, NAD+ oxidizes this) to form the beta-keto thioester intermediate (we now have 2 carbonyls) 5. C-C break using cysteine residue to expel Acetyl-CoA as LG. (so we're removing acetyls on thioester end AT THE LEGIT END) 6. now the new end is enzymatically converted to acetyl thioester again to repeat cycle :)

Answer 45

R-C(=O)-OR'

Answer 46

Soaps are naturally occurring, while detergents are synthetic

Answer 47

The esters in fatty acids are broken by NaOH, to create soaps. (BASE hydrolysis) This means that soaps are metal (sodium) salts of fatty acids, with COO-Na+)

Answer 48

Because at high [Na+], sodium salts are insoluble, then you cause a salt precipitate (aka, Na+ won't be off on its own)

Answer 49

The hydrophobic tails of individual soap molecules are attracted to each other via hydrophobic forces, and so they come together to make these spherical structures. Hydrophobic grease gets in between the leaky pores (because the heads repel each other slightly), and then you add water to wash it away

Answer 50

The carboxylates of salts precipitate out in the presence of polyvalent ions (Ca2+, Mg2+, Fe3+, etc.) and these are present in hard water. So you'll just get soaps precipitating out. Using detergents, because they have hydrophilic heads that are not carboxylate (Anionic, Cationic, or Non-ionic). But the hard-water ions still mixed with clay and mud to leave laundry grey, so they used Phosphate-based Additives (interact with hard-water ions like Mg binds as cofactors). Or use the modern alternative of ^^ using Silicates.

Answer 51

A CO2 carrier. aka, a carbonyl transfer agent. Aka, carboxyl group gets passed onto it, and then it passes it on to something else (to acetyl coA to make malonyl thioester/coA)

Answer 52

It's the conjugate addition to alpha,beta-unsaturated carbonyl

Answer 53

1 ATP, and 2 NADPH

Answer 54

1. Condensation 2. Reduction of carbonyl 3. Dehydration 4. Reduction of alkene

Answer 55

1. Acid-catalyzed, self-polymerization of propylene (electrophilic addition to alkenes). Done multiple (to ~12 Cs) times (grab a proton, carbocation gets formed, double bond attacks) 2. EAS rxn. Where = on tail reacts with benzene 3. Sulfonation (EAS)-- to yield the sodium sulfonate salt on benzene, when treated with SO3/H2SO4 then a base.

Answer 56

- most stable carbocations are obtained from the addition of the electrophile to the ortho and para positions. - best because less steric interference - when the carbon with the alkyl group has the positive charge, that's the best resonance structure - EDGs are therefore called "ortho-para directors" because they direct the electrophile to that position. - EWGs are "meta directors". (eg, NO2)

Answer 57

- usually quaternary ammonium salts (+charge N, with 4 C coming off it-- or has the potential to do so

Answer 58

- hydrophilic head without any formal charge (usually with ethoxylated alcohol)--like /\O/\O/\O a bunch of times

Answer 59

- glycerol attached to two fatty acids (the tails) and a monoester of phosphoric acid. - the fatty acids are saturated and unsaturated, which makes phospholipids give membrane a fluid-like, semi-permeable quality. - phospholipids have the phosphatidic backbone esterified to a OR at the phosphate (of the phosphoric acid).

Answer 60

- no because, although their heads are still hydrophilic, they have 2 tails that fit nicely together, while still maintaining good distance btwn the heads - because both the intracellular and extracellular environments are aqueous

Answer 61

- a C20 prostanoic acid skeleton (has C7 carboxylic acid chain + cyclopentane ring + C8 chain) - only seen in the presence of physiological triggers (infection, injury) which is when they'll bind to receptors to cause inflammation, etc. - made from oxidation of arachidonic acid by enzyme COX (Cyclooxygenase) using O2. - inhibited by COX2 - also inhibited by NSAIDs which inhibit the biosynthesis of prostaglandins

Answer 62

- seen in response to allergens (so they'll trigger allergic responses) - made from arachidonic acid by leukocytes. - the first step being the EPOXidation of arachidonic acid by enzyme 5-lipoxygenase - inhibit using 5-lipoxygenase inhibitor Zyflo. Or prevent leukotriene from binding to receptor by treating with receptor Antagonist (antagonists inhibit action).

Answer 63

EAS creates a resonance-stabilized carbocation. SN2 doesn't, it just has a quick transition state where the conformation changes btwn R and S. NuAS= Claisen=carbanion attacks

Answer 64

Compounds that contain multiples of 5 Cs (aka, multiple of the Isoprene unit-- but isoprene itself isn't in the terpene compound, it just forms it, because once they're linked they undergo chemical transformations) - they are named according to how many 10C units they have. So Monoterpene is 10C (2 isoprene units-- 1 head-tail linkage). - Sesquiterpene is 15C with 3 isoterpene units (only need TWO H-Ts) - 30C=triterpene= is two sesquiterpenes linked TAIL-TAIL - 40C= Tetraterpene=2 diterpenes linked TAIL-TAIL

Answer 65

DMA-OPP acts as Electrophile because it forms a stable carbocation when it loses OPP. IPP-OPP acts as a Nucleophile because it will not ionize because it would give an unstable carbocation, so we just use its normal form as the Nu. - IPP-OPP's = head attacks DMA's tail = to form a new TRANS bouble bond

Answer 66

Use IPP as another Nu to attack the monoterpene. Now do reductive dimerization to join two 15Cs together, via Tail-tail. The OPPs on each tail leave and that's where the bond will form.

Answer 67

- made from beta-keto thioester reacting with acetyl thioester (it attacks the beta-keto group) to form a C6 compound, which must undergo a few enzyme-catalyzed reductions (achiral--> chiral; hydride; reduction) to get to Mevalonic Acid. Mevalonic Acid is then turned into IPP via 3ATP, -PPi, -CO2. Then isomerization can turn IPP-OPP to DMA-OPP, favourable.

Answer 68

- FLAT tetracyclic fused-ring system (three 6-membered rings, one 5-membered ring), with rings fused in TRANS (can see this bc the CH3 and H are in trans, both in axial)

Answer 69

- squalene(30C)--->lanosterol--> any steroid basically - Squalene (in its crimped up folding -- is in CHAIR-BOAT-CHAIR) is enzymatically oxidized to an epoxide. The epoxide is strained, so opens very easily in presence of acid; concertedly, one of its alkenes attacks protonated epoxide. Then a whole bunch of carbocation intermediate steps until Protosteryl Cation undergoes 1,2-hydride shifts and 1,2-alkyl shifts (= movement of H and CH3 along with their bonding electrons).

Answer 70

- Vitamin A (Retinol) is fat-soluble, coming from provitamin beta-carotene - Retinol oxidized to 11-CIS-Retinal (Vitamin A aldehyde), which forms an imine (Schiff base) with an NH2 group in Opsin protein ==> Rhodopsin. - Light absorption in the Retinal-Opsin complex causes double-bond isomerization and release of 11-TRANS-retinal from enzyme.

Answer 71

The phenolic OH group. - it easily loses the H atom (e- + proton) to give resonance-stabilized free radical. And this H goes and quenches other free radicals that may cause damage. - "radical scavenger" - since Vitamin E radical (Ar-O) is stable and hindered by the methyl groups around its phenol group, it does not cause damage. (only its tail is a terpene)

Answer 72

enol: alkene+alcohol "alkene-ols" enolate: alkene+alcohol deprotonated (ionized)

Answer 73

Because detergents are usually salts of strong acids and conjugate bases of strong acids are not basic. So that's why soaps dissolved in water will actually be basic, because they're salts of weak acids.

Answer 74

Remains in aqueous solution.

Answer 75

N 1 in pyrimidines (U, C, T -- as long as the backbone rings are same, stuff can be added to OG structure) N 9 in purines (A, G) - they'll link to ribose or deoxyribose to make ribonucleosides or deoxyribonucleotides (base+beta sugar)

Answer 76

nucleosides (beta sugar+base) + 1 or more phosphates attached to one or more of the OH groups - sugar numbered with prime numbers nucleic acids: phosphate diesters of nucleotides

Answer 77

- molecules binding with H-bond donors and acceptors in the major and minor grooves (ex, Netropsin antibiotic--minor groove, or a protein) - intercalation: molecules inserting themselves in btwn the base pairs (ex, Nogalamycin antibiotic)

Answer 78

N-glycosidic linkages, and phosphate esters

Answer 79

Because RNA is especially susceptible to strand cleavage under Basic conditions, and is accelerated by the presence of divalent cations. bc of oxy @2'

Answer 80

- melt DNA to Tm (where half of the DNA are ss) - anneal primer onto template strand (so now it has a 3'OH on which to add its nucleotides) - DNA Polymerase synthesizes 5'->3' - melt again and do more and more from the template strands

Answer 81

- prepare 4 rxn mixtures all containing: primer, DNA template, DNA Polymerase, buffer, Mg2+, all 4 dNTPs, a small amount of one ddNTP) - the one ddNTP terminates elongation bc it doesn't have 3'OH.

Answer 82

- all dideoxy compounds are 32P-labelled on the P attached to the 5'O, the P that will be incorporated into the chain - separate by gel electrophoresis (separated by length, shortest one closest to anode-- aka, migrated the most) - the decay of the 32P exposes the film and shows band pattern - REMEMBER, what you get from the gel is the COMPLIMENTARY STRAND - ex, in the A rxn, termination can only end with a ddATP - the ones in primers don't get labeled/terminated, but when you're asked for sequence, include this!! (its complement) - if A for example was at the end, you'd have one complete strand with the label, and one complete strand without the label

Answer 83

- only ONE rxn needed! - you have 4 ddNTPs fluorescent dyes specific for each base, so each of A, T, C, and G emit different wavelength maximums, which are used for reference. All the dyes are based off Rhodamine Dyes - put in capillary gel electrophoresis (short fragments migrate furthest to anode, aka reach the detector first) and as they travel, they're detected by fluorescence (laser excitation) at other end of capillary - remember, you get the complementary! - if asked the sequence, do the complimentary of PRIMER too!!!!

Answer 84

``` DMT= 5'OH Protecting Group (looks like 3 benzs, 2 having MeO attached) DMT= dimethoxy ---- we're not using trimethoxy because too acid-labile (come off too easy, but we want PG to stay on). not using monomethoxy because you'd need a stronger acid(too hard to remove) ``` TCA removes DMT. The product of DMT that is formed after deprotection will absorb visible light bc rings are conjugated + carbocation (triarylmethane chromophores).

Answer 85

- a controlled pure glass polymer w/ COOH using DCC, forming an ester - the DMT group is more acid-labile than this ester, so when TCA comes to take DMT off, this ester is safe

Answer 86

- solid-phase - protect 5'-OH w/ DMT, then protect 3'-OH with glass polymer+COOH (ester) using DCC - use phosphoramidite (+ tetrazole (weak acid that will protonate the N of the phosphoramidite) for COUPLING RXN, then oxidize Phosphite product to phosphate (PIII->PV oxidation state). - coupling rxn: via an acid-catalyzed substitution where the amine is replaced by the 5'-OH of our suga (aka, adds another sugar onto 5' OH -- 3' of new). The acid in this rxn must be very weak so as to not remove DMT or hydrolyze the ester - oxidation using I2/H2O (iodine) and pyridine - deprotect using TCA - either repeat or cleave.

Answer 87

YAH. so =N- is sp2-hybridized!

Answer 88

Cyanoethyl is a 'permanent PG' on the O of the P of phosphoramidite all the way til the end of the synthesis when desired length is reached because the phosphate O- could potentially act as a Nu.

Answer 89

- the cleavage of product from insoluble polymer and removal of the PGs are done together using aqueous ammonia (basic) - the cyanoethyl group is lost in a beta-elimination rxn - a strong acid could ruin phosphodiester and N-glycosides

Answer 90

UV-A -- causes some DNA damage UV-B -- major mutagenic/lethal part of sunlight UV-C -- deadly (high energy) - sunscreen should have UV-A and UV-B covered because our ozone doesn't really absorb a lot of those, but absorbs all of UV-C.

Answer 91

Direct DNA damage:- formation of T-T dimers: two adjacent thymines undergo a [2+2] photocycloaddition rxn forming a 4-membered cyclobutane ring, which creates a kink in the double helix which affects replication Indirect DNA damage: UV light causes free radicals to form which wreck DNA

Answer 92

One of its oxygen metabolites, an epoxide. Ironically, the body oxidizes benzene to make it more suitable for excretion. Toluene because the benzylic carbon oxidizes before the aromatic ring does -- better clearance from body because more water-soluble.

Answer 93

Burning of fats at high temps forms polyaromatic hydrocarbons (PAHs). They are large, planar and hydrophobic and thus can intercalate DNA and then react with it --> mutation to nucleic acid Also burning meat creates heterocyclic aromatic amines (HAA) Aflatoxin released from fungus

Answer 94

1. Drug discovery and preclinical evaluation(in vitro testing, ADMET studies in vivo -- if passed, apply for investigational new drug (IND)) 2. Clinical Evaluations -- if passed, apply for NDA (new drug approval) 3. FDA approval, marketing, and post-market surveillance/pharmacovigilance

Answer 95

Method 1: extract from natural products (ex, opiates, taxol, penicillin) Method 2: Structure-Activity Relationship (SAR) -- evaluate effect on activity of structural changes to already existing molecule Method 3: Structure-Based (Guided) Drug Design -- virtual screening/in silico technique where computers design drug to see if they react with desired target Method 4: High-Throughput Screening (HTS) -- rapid screening of large libraries of compounds. See if you get a 'hit' which are developed into 'lead compounds'/potential drug

Answer 96

Therapeutic Index: LD50/ED50 (aka, safety/efficiency) - LD50= how much is needed to kill 50% of people - ED50= effective dose as a drug

Answer 97

Phase 1: safety, ADMET, side effects (1.5 yrs, <100 healthy volunteers), safe dosage range Phase 2: effectiveness, and short-term side effects (1.5 yrs, <500 volunteers with targeted disease or symptom) Phase 3: effectiveness, long-term side effects, optimum dosage, optimum route of administration (1.5 yrs, thousands of volunteers with targeted disease or symptom) - phase 2 and 3 must be double-blind, placebo and randomized - each phase requires approval from FDA to progress. But could fast-track if dealing with drug for orphan disease (no known treatments yet)

Answer 98

Use it for something other than its intended effect

Answer 99

Reduced form of folic acid (vitamin B9) Bacteria need it for DNA synthesis. Humans can't synthesize folic acid so we're safe from the sulfa drugs. We just get it from diet instead. - bacterial cells can't get it across cell membrane so synthesize DHF (dihydrofolate) from PABA, pteridine derivative and glutamic acid, which need to be linked. 1. Link pteridine derivative to PABA (amine from PABA replaces OH LG by 2P on pteridine via SN2) 2. amide bond formed btwn amino group of glutamic acid and carboxylate from product in 1 (using ATP to activate carboxylate by forming a mixed anhydride) - then reduce DHF to tetrahydrofolate IN BACTERIA CELLS The deprotonated Sulfanilamide bacteriostatic/antibacterial drug inhibits this process because it is similar to PABA, so it acts as a substrate analog, competing for the enzyme. so no tetrahydrofolate so no good DNA synthesis of bacteria, so bacteria cannot grow/reproduce. aka, it inhibits the enzyme needed by bacteria to synthesize folic acid

Answer 100

bacteriostatic because it stops bacteria from growing. Comes from Prodrug which was reduced in liver to create this. needs to be deprotonated to function (because PABA is deprotonated at neutral pH), but its pKa is 10.43 so only 1/1000 is deprotonated form. if you lower the pKa this could help but now it can't get through cell membrane (must be neutral to cross). so Scientists made a better drug by adding a substituent (EWG) to the N which has optimal pKa of 5

Answer 101

1. drug or its precursor is administered to patient (consumed, injected, applied) 2. The chemical concentrates at tumour site. affected area is irradiated with appropriate wavelength light 3. the drug is excited which eventually leads to tissue destruction, because Reactive Oxygen Species (ROS) were created

Answer 102

singlet oxygen, O2-, HO•, HOO•, H2O2 they are oxidants that will destroy virtually all biomolecules - normal ground-state oxygen is in triplet state. In the presence of the proper energy, this can be excited to form singlet oxygen. this excitation comes from Energy Transfer mechanism from a photosensitizer (PDT drug, ex. photofrin). - Ps is shot by laser and excited to 3Ps (ISC happened). Triplet states like to interact with other triplet states, which makes 3O2 turn into 1O2 - this process is catalytic, and drug is regenerated - so you want this to treat cancer because it'll kill off the tumour cells

Answer 103

- long elimination half-life (21 days can't go in sunlight, and need to be protected for 1-3 months) - cannot be used for deeply penetrated tissues, because the light doesn't go that far, so we need photosensitizers that absorb at longer wavelengths. but then you also need them to be powerful enough (enough energy)

Answer 104

False. Tautomers are constitutional isomers.