Exam 1 Flashcards by Sarah Johnston

What is a drug

An exogenous substance which has a physiological effect when introduced into the body

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What is pharmacology

The branch of medicine concerned with the uses,

effects, and modes of action of drugs

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What is pharmacokinetics

The study of how drug concentration varies with time
after administration, and how long and where it persists
in the body over time.

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Pharmacokinetic parameters are affected by what four processes

Absorption
Distribution
Metabolism
Excretion

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What is pharmacodynamics

The study of the relationship between drug concentration
in the body and the response of the body to that
concentration of drug

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Fundamental unit of life

Cell

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What is the most common type of drug target

Receptors

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What is the importance of a cellular response

Affects the physiology and health of the individual

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Four major types of receptors

Ligand gated ion channels
G protein receptors
Receptor tyrosine kinases
Nuclear receptors

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What non-receptor macromolecules can also be drug targets

Nucleic acids
Structural proteins
Enzymes
Ion channels
Cytokines

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Drugs are categorized into families based on what three things

Structural characteristics of ligand or target
Signaling pathways affected by ligand engagement
Level of organization targeted by the drug (ex. molecule, organelle, cell, tissue)

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What is a structure activity relationship (SAR)

the relationship
between the chemical or 3D structure of a molecule and
its biological activity.

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How would you change the “structure” of a drug to alter

its interaction with a target?

Modification of covalent bonds and atomic composition
of a drug can alter its ability to participate in non-covalent
interactions with its target.

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What are the four important non-covalent interactions between drug and target

– Number of H-bond donors or acceptors
– Number and type of charge
– Hydrophobicity
– Polar bonds

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What are some different types of “activities” that are

affected by the chemical structure of a drug?

-Target potency
-Target selectivity
-Modifications to reduce toxicity
-Scaffold hopping to allow patentability
-Physical properties and formulation
-Modifications for bioavailability
Modifications to modulate metabolism
-Receptor drug interactions

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Define principle

a fundamental truth or proposition that serves as
the foundation for a system of belief or behavior or for a chain
of reasoning

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What is the central dogma?

DNA –transcription–> RNA –translation–> Protein

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What are the three building blocks of DNA

Sugar: Deoxyribose
Phosphate
Bases (Adenine, Guanine, Thymine, Cytosine)

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What is the structural difference between deoxyribose and ribose sugar

Deoxyribose: 2’ carbon has H
Ribose: 2’ carbon has OH

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Which nucleotide bases are purines

Adenine and guanine

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Which nucleotide bases are pyrimidines

Thymine and cytosine

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What is a nucleobase

a nitrogenous heterocycle

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What is the importance of nucleobases

The endocyclic nitrogens
are basic and can function
as hydrogen bond
acceptors

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What is the difference between nucleosides and nucleotides

Nucleosides only contain sugar and base, they lack phosphate

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Nucleotides exist in what state

In equilibrium between various phosphorylated forms

What enzymes add phosphate groups

Kinases

What enzymes remove phosphate groups

Phosphatases

Why are di- and triphosphate analogs involved in energy, metabolism, and cell signaling?

Phosphoanhydride bonds are very high energy and cyclization makes them key second messengers

What is the name of the important bonds in single stranded DNA

phosphodiester bonds

Single stranded DNA runs in which direction

5'--> 3'

What is a polymer of nucleotides

DNA

What causes the antiparallel nature of each DNA strand?

Directionality of phosphodiester linkages

What forms between nucleotide base pairs

Dimers (H-bonding)

What happens if drug binding disrupts H bonding in DNA structure

Alters replication and transcription

What phase of the cell cycle is characterized by pre-DNA synthesis?

What phases of the cell cycle are encompassed under "Interphase"

G1 + S + G2

What part of the cell cycle does DNA synthesis occur?

What part of the cell cycle does post-DNA synthesis occur?

List the cell cycle phases from longest lasting to shortest

G1>S>G2>M

What is the importance of major and minor grooves in DNA

Allow for interactions with proteins such as transcription factors

Describe the helix-turn-helix motif

- Found in transcription factors - 1st helix stabilizes interaction with DNA - 2nd helix often called "recognition helix" because it interacts with base pairs in the major groove

Describe the zinc finger motif

- Found in transcription factors - Arg 46 and His 49 form sequence (specific contacts) - 3 nonspecific contacts between PO4 groups and side chains

What are the three steps of transcription

Initiation Elongation Termination

What is mRNA

single stranded messenger RNA that serves as the template for protein biosynthesis

True or false: mRNA has secondary structure

True

What is tRNA

Transfer RNA transfers amino acids during protein synthesis. Matches anticodon to codon on mRNA

tRNA forms what type of bond with amino acids?

Ester bond

What are ribosomes composed of

rRNA and protein

What is the site of protein synthesis

Ribosome

What are the two ribosomal subunits found in prokaryotes

30S/50S

What are the two ribosomal subunits found in eukaryotes

40S/60S

Do eukaryotes or prokaryotes have a larger ribosome

Eukaryotes

What are two examples of cancer drugs that form a covalent bond with DNA

``` nitrogen mustards (melphalan) Platinum complexes (cisplatin) ```

Melphalan and Cisplatin are alkylating agents that typically attack what specific nitrogenous base (at what site too)

N7 of guanine that is exposed in the major groove

Why is alkylation important in cancer drugs

Alkylation adds on alkyl adducts to DNA, which prevent replication and leads to cell cycle arrest or cell death. Interrupts normal functions of enzymes involved in DNA replication

What non-covalent forces contribute to DNA-drug binding

Van der Waals H bonding Electrostatic/ionic Hydration/dehydration of binding site

Intercalators like doxorubicin use what non-covalent force to intercalate between base pairs?

Van der Waals

Minor groove binders like distamycin use what non-covalent force to bind adenine and thymine rich regions?

H bonding and hydrophobic interactions

What dual binding molecule intercalates and binds to minor groove to cleave one or both DNA strands?

Dynemicin A

What are nucleic acid analogs

Substrates or inhibitors of various enzymes that metabolize normal nucleic acids

What must be done to nucleoside analogs to affect DNA and RNA synthesis

Converted to active forms as triphosphates

Chemical modifications can be made to functional groups at various parts of the nucleotide, what can be done to the base?

Halogenation

Chemical modifications can be made to functional groups at various parts of the nucleotide, what can be done to the sugar?

Hydroxylation/dehydroxylation

Chemical modifications can be made to functional groups at various parts of the nucleotide, what can be done to the phosphate?

Protection by polar groups

Retroviruses need to replicate their RNA. What enzyme do they use?

Reverse transcriptase

What does the enzyme reverse transcriptase do?

Makes DNA from an RNA template

Can reverse transcriptase be found in normal human cells?

Zidovudine is an antiviral that acts as a reverse transcriptase inhibitor. How does this medication work?

Its sugar has been dehydroxylated and in place of the OH group on 3' end it has an azido group. The azido group prevents DNA chain elongation. HOWEVER it can be phosphorylated on 5' end for bioactivation

Adefovir is an antiviral that acts as a reverse transcriptase inhibitor. How does this medication work?

The sugar ring is opened/eliminated, preventing DNA elongation during replication. The phosphate has been replaced with a phosphonate, increasing stability

Remdesivir is an antiviral. What characteristics help it to prevent DNA replication?

It is a prodrug with a 1' cyano group and altered base

How do anticancer agents work and why?

Cancer cells divide rapidly which required DNA synthesis. by blocking DNA synthesis, S phase of cell cycle is stopped.

At what phase of the cell cycle do organelles and cytosolic components duplicate and centrosomes begin to replicate?

At what phase of cell cycle is DNA replicated?

At what phase of cell cycle is cell growth continuing, enzymes and proteins are synthesized and centrosome replication is completed?

Fluorouracil is an anticancer agent. What characteristics help it treat cancers?

It is a pyrimidine analog. It is basically uracil that has undergone halogenation (addition of a fluorine)

Fluorouracil (5-FU) can be converted into FdUMP, FdUTP, and FUTP. What does having multiple mechanisms of action do for this molecule?

It allows it to inhibit thmidylate synthase, causes DNA damage, and causes RNA damage respectively.

Cytarabine is an anticancer agent. What characteristics help it to treat cancers?

It is a dehydroxylated isomer of cytidine. It causes DNA damage

Gemcitabine is an anticancer agent. What characteristics help it to treat cancers?

It is an analog of cytidine formed by halogenation. Causes DNA damage

What is a catalyst

A substance that increases the rate of a chemical reaction, without itself being changed during the reaction

What is an enzyme

a protein that acts as a biological catalyst

Describe lock and key model

The enzyme and substrate | fit together

Describe conformation selection model

The conformation of the enzyme varies, one conformation recognizes the substrate (ligand)

Describe induced fit model

Binding the substrate induces a change in the enzyme

Role of oxidoreductases

Catalyze oxidation/reduction | reactions; transfer of H and O atoms or electrons from one substance to another

Role of transferases

Transfer of a functional group from one substance to another

Role of hydrolases

Formation of two products from a | substrate by hydrolysis

Role of lyases

Non-hydrolytic addition or removal of | groups from substrates

Role of isomerases

Intramolecule rearrangement ie. isomerization

Role of ligases

Join together two molecules

DNA polymerases requires what cofactor?

Magnesium ions

Exam 1 Flashcards

(90 cards)