Lecture 5

Question 1

Cisplatin has what metal in it

Auranofin has what

And cardiolyte has what

Slide one structures of cisplatin and auranofin and cardiolyte

Answer 1

Pt
gold (au)
Tc

Know structures

Question 2

Why does gadolinium work well for contrast in MRI imaging

Answer 2

It is pheromagmetic

Question 3

What is the difference in cisplatin vs carboplatin

Answer 3

Cisplatin has more side effect because it’s less selective for cancer cells

Carboplatin more selective (but works the same)

Question 4

What is the activation mechanism of cisplatin

Answer 4

Outside the cell (in blood) where [cl] is high, the cisplatin is inactive

Through passive diffusion it goes into cell low cl concentration

it gets hydrated and one of its cl is replaced by water

When both the cl are gone that’s the active form of cisplatin

Question 5

What is required for cisplatin to react with DNA

Answer 5

Two adjacent Guanine groups (to line up their guanidines)
ex. C-G
C-G

That way it can form a bend in the dna by interacting with the G groups

Question 6

What does cisplatin do to the DNA

Answer 6

it forms a bend in the dna by interacting with the G groups

That way it interferes with dna transcription and replication

Question 7

What distinguishes between hard and soft metals

Answer 7

The oxidation state

Question 8

What are the hard metal and what do they bind to

Answer 8

Fe3+, ca2+

Na+, K+, Mg2+

Bind to oxygen

Question 9

What are the borderline/intermediate metal and what do they bind to

Answer 9

Fe2+, ni2+, zn2+, Co2+, Cu2+

Bind to nitrogen’s

Question 10

What is special about imidzole in terms of metal binding

Answer 10

Binds tightly to. The 2+ forms of Ni Zn Co

Question 11

What are the soft metal and what do they bind to

Answer 11

Cu+
cd2+, pt2+, pb2+, hg2+

Bind sulfur (usually cysteine)

Sometimes bind nitrogen

Question 12

What can side chains of protiens do in terms of metals

Answer 12

They can act as ligands for the metals

Question 13

What are the types of metal side chain interactions

That cysteine , histidine, and aspartate can make

Answer 13

Monovalent (ex. S of cysteine binds one metal)

Divalent ( S binds two metals)

Eta nitrogen (one metal binds the eta N of his)

Delta nitrogen (one metal binds to the delta N of his)

Monodentate: (one metal bound to one oxygen of asp)

Bidentate: (one metal bound to two oxygen of asp)

Bidentate bridging: two metals bound to one each oxygen of asp

Question 14

What is an example of a protien that binds soft metals

What does it do

Answer 14

Metallothionein

Binds zinc tightly outside the cell (in blood,)

Dextoxifies heavy metals like cd pb, mercury

Involved in zinc and copper metabolism

Question 15

What are hard hard bonds

What special about calcium in these bonds

Answer 15

Ex. Calcium to oxygen

Calcium has a wide range of distances if can form interactions with compared to other metals

Has both bidentate and mono dentate binding

Question 16

What are shared ligands in hard hard bonds

Answer 16

When one hard metal is bound to one oxygen in a side chain and another metal is bound to the other

This sharing causes bidentate bridging

Question 17

What effect does the size (ionic radius) have on the # of interactions a metal can make

Answer 17

Large radius, more interactions

Larger radius, the easier for water to be stripped off but the smaller metal keeps water on more strongly (water needs to be stopped of the metal before the metal can bind to a protein)

Question 18

How many interactions can Mg, Ca, Al and Ga make

Answer 18

6, 7.3, 5.3, 4.6

Question 19

coordination numbers 3,4,5,6,7 line up with which geometry and give examples of the metals that make these geometry’s

Answer 19

3: trigonal planar, pyramidal, T-Shaped

4: square planar (cisplatin-pt2+, ni2+, cu2+ albumin)
tetrahedral (zn2+)

5: square pyramidal (Cu2+ prion), trigonal bipyramidal

6: octahedral (fe3+,mg2+)

7: pentagonal bipyramidal (ca2+)

Question 20

pentagonal bipyramidal (ca2+) interaction is

Answer 20

Planar

Question 21

What is the pentagonal bipyramidal structure that the ca2+ binds to

Answer 21

The EF hand protien

Question 22

What is the EF hand protien

How many positions are there and what is in each position

Answer 22

It’s a structural and sequential motif

Has a EF hand binding loop with 12 potitions

In positions 1,3,5,7,12: there are oxygens from asp or glu

In position 6: gly

In position 9: water

Ca binds to the oxygens and water

Question 23

What is transferrin (Tf)

Answer 23

It’s a protien that transports fe3+ through the body

Binds tightly to fe3+ but not fe2+

Question 24

What happens to transferrin if fe3+ gets reduced to fe2+

Answer 24

The affinity of Tf for the fe ion is decreased since transferrin only binds fe3+

Question 25

What type of binding does transferrin do to fe3+

Answer 25

Octahedral (because it has a coordination number of 6)

Binds it’s carbonate group to fe through bidentate (hard metal)

Question 26

What is different in the binding of ca2+ and fe3+

Answer 26

Fe3+ has restricted distances in its octahedral binding

But ca2+ is a promiscuous binder (binds with large distances)

Question 27

What are the factors that make a metal ion know to bind to a specific protien and not another

Answer 27

If it’s hard soft or intermediate (does it like the ligands in the protein)

The size of the metal cation (is its ion is radius too big or too small to fit in the binding site?)

The preffered coordination chemistry (tetrahedral vs square planar) pt4+ is tetrahedral but 2+ is square planar

The rate and energetics of dehydration

The availability of the metal (ex. Ca not toxic, so as ca gets higher, muscles contract and proteins react and get active so they bind ca in concentration dependent manner)

Question 28

Where is fe3+ and where is fe 2+, what does this mean for binding

Answer 28

Outside the cell

Inside the cell

This means that the availability of both forms is different depending on the location, which changes which proteins bind

Question 29

Where is fe3+ and where is fe 2+, what does this mean for binding

Answer 29

Outside the cell

Inside the cell

This means that the availability of both forms is different depending if the location which changes which proteins bind

Question 30

If fe is more abundant than ca, why did evolution choose ca for most processes?

Answer 30

Because fe ionic radius is lower and has less coordination sites

Whereas ca2+ is a promiscuous binder and has higher ionic radius