4_5_AminoAcids.pptx

Lecture 4-2 (9/14/20)

OUTLINE

Amino Acids

– Definition

• The 4 S’s

• Common Properties

• Five Classes

– Hydrophobic–aliphatic [6]

– Hydrophobic–aromatic [3]

– Special–sulfur [2]

– Hydrophilic–polar [4]

– Hydrophilic–charged [5]

• Other amino acids

• Linking amino acids

• Acid/base properties

– Titrations

– Isoelectric point

• Electrophoresis

Amino&Acids:&

Building&Blocks&of&Protein

Definition

• Proteins are linear heteropolymers of L-

-amino

acids.

• These are organic acids with an amino group at the

-position, or the 2-position.

• The amino group is basic and the carboxylate group

is acidic (of course). The R-groups are different.

C–C–C–C–C–Functional

e d g b a Group (COO

–

)

6 5 4 3 2 1

Amino&Acids:&

Building&Blocks&of&Protein

Definition

• Proteins are linear heteropolymers of L-

-amino

acids.

• These are organic acids with an amino group at the

-position, or the 2-position.

• The amino group is basic and the carboxylate group

is acidic (of course). The R-groups are different.

C–C–C–C–C–Functional

e d g b a Group

6 5 4 3 2 1

Amino&Acids:&

Building&Blocks&of&Protein

The 4 S’s: Size

3 Å diameter

8 Å diameter

Amino&Acids:&

Building&Blocks&of&Protein

The “L” configuration means

levorotary, or rotates polarized light

counter-clockwise, or left handed

In R/S, this is what?

The 4 S’s: Shape

Here we have to discuss stereochemistry: particularly

what is meant by the “L” configuration

①

②

③

Clockwise is R

Counterclockwise is S

R = D

S = L

Recall:

What is the relationship between

R/S and D/L?

Amino&Acids:&

Building&Blocks&of&Protein

The 4 S’s: Shape

Clockwise is R

Counterclockwise is S

R = D

S = L

Fisher Projection

1. Carbon chain vertical with functional group at top

2. At each carbon the vertical bonds to carbons are

behind, projecting away from the viewer

3. At each carbon the horizontal bonds are projecting

towards the viewer

4. If the functional group (not H) is to the left it’s L

5. If the functional group (not H) is to the right it’s D

(R)

(S)

Amino&Acids:&

Building&Blocks&of&Protein

The 4 S’s: Stability

All amino acids are stable to acid, base, and heat

Exceptions are:

1. Trp (oxidation)

2. Cys (oxidation)

3. Asn (deamination)

4. Gln (deamination)

àN-formyl-kynurenine

àDisulfides (R’-S–S-R”)

àHydrolysis of amide: Asp

àHydrolysis of amide: Glu

Amino&Acids:&

Building&Blocks&of&Protein

The 4 S’s: Solubility

• As$zwitterions,$most$amino$acids$are$soluble$to$

some$degree.$$But,$depending$on$the$R$group$they$

are$less$soluble$or$more$soluble

• The$general$grouping$puts$10$as$ less $soluble:

A,$V,$L,$I,$P,$W,$Y,$F,$M,$C

• and$10$as$more$soluble:

G,$S,$T,$N,$Q,$D,$E,$H,$K,$R

Amino&Acids&Have&Three&Common&Properties

• Groups Attached to the α Carbon. The α carbon

always has four substituents and is tetrahedral.

– an acidic carboxyl group connected to the α carbon

– a basic amino group (1°or 2°) connected to the α carbon

– an α hydrogen connected to the α carbon

– A fourth substituent called an “R group.”

• All Amino Acids are chiral with the L configuration

(except glycine where the R-group is a hydrogen).

• Acid/Base properties:

Net Charge = +1

Net Charge = 0

Net Charge = –1

Zwitterion

What is the

predominant form

at physiological

pH (7.4)?

= ~2.3 pK

= ~9.6

Amino&Acids&Have&Three&Common&Properties

• Groups Attached to the α Carbon. The α carbon

always has four substituents and is tetrahedral.

– an acidic carboxyl group connected to the α carbon

– a basic amino group (1°or 2°) connected to the α carbon

– an α hydrogen connected to the α carbon

– A fourth substituent called an “R group.”

• All Amino Acids are chiral with the L configuration

(except glycine where the R-group is a hydrogen).

• Acid/Base properties:

Net Charge = +1

Net Charge = 0

Net Charge = –1

Zwitterion

What is the

predominant form

at physiological

pH (7.4)?

= ~2.3 pK

= ~9.6

Amino&Acids:&Classification

• The 20 amino acids found in proteins can be

placed in five families based on the physical and

chemical properties of their R groups:

• Hydrophobic, aliphatic (6)

• Hydrophobic, aromatic (3)

• Special (hydrophobic/hydrophilic)(2)

• Hydrophilic, polar (4)

• Hydrophilic, charged (5)

Table:

Name 3-letter

1-letter

abundance

in proteins

Year

discovered

NOTES

Structure

mnemonic

device

Essential

✓

Must KNOW

Amino&Acids:&Classification

Hydrophobic, aliphatic

Glycine Gly G 1820 7

Smallest, not chiral H

Alanine Ala A 1888 8

Foundational for ~10 other AA Methyl

Valine Val V 1856 7

isopropyl V-shaped

Leucine Leu L 1819 10

Most abundant, dominant Ala + Val

Isoleucine Ile

1904 6

Two chiral centers (L & D) Val + Me

Proline Pro P 1901 5

Only imino acid (2° amine); special

bonds in proteins; is modified by hydroxyl

5-membered ring;

same #C’s as Val

Pro

Name 3-letter

1-letter

abundance

in proteins

Year

discovered

NOTES

Structure

mnemonic

device

✓

Amino&Acids:&Classification

Hydrophobic, aliphatic

Glycine Gly G 1820 7

Smallest, not chiral H

Alanine Ala A 1888 8

Foundational for ~10 other AA Methyl

Valine Val V 1856 7

isopropyl V-shaped

Leucine Leu L 10

Most hydrophobic Ala + Val

Isoleucine Ile

Two chiral centers (L & D) Val + Me

Proline Pro P 5

Only imino acid (2° amine); special

bonds in proteins; is modified by hydroxyl

5-membered ring;

same # as Val; 3C

Pro

Name 3-letter

1-letter

abundance

in proteins

Year

discovered

NOTES

Structure

mnemonic

device

✓

Gavlip family

1819

1904

1901

Amino&Acids:&Classification

• The 20 amino acids found in proteins can be

placed in five families based on the physical and

chemical properties of their R groups:

• Hydrophobic, aliphatic (6)

• Hydrophobic, aromatic (3)

• Special (hydrophobic/hydrophilic)(2)

• Hydrophilic, polar (4)

• Hydrophilic, charged (5)

Gavlip family

Amino&Acids:&Classification

Hydrophobic, aromatic

Phenylalanine Phe F 1879

aromatic

Phenyl+Ala

Tyrosine Tyr Y 1846 3

aromatic, can ionize; pK

≈10.1

amphipathic

p-phenol+Ala

Tryptophan Trp W 1901 1

aromatic & fluorescent;

least abundant, largest AA

Indole+Ala

Name 3-letter

1-letter

abundance

in proteins

Year

discovered

NOTES

Structure

mnemonic

device

✓

Recall:

Absorb

UV light

max

Extinction

coefficient

(x10

-3

)

259 0.7

278 1.1

279 5.2

Amino&Acids:&Classification

Hydrophobic, aromatic

Phenylalanine Phe F 1879

aromatic

Phenyl+Ala

Tyrosine Tyr Y 1846 3

aromatic, can ionize; pK

≈10.1

amphipathic

p-phenol+Ala

Tryptophan Trp W 1901 1

aromatic & fluorescent;

least abundant

Indole+Ala

Name 3-letter

1-letter

abundance

in proteins

Year

discovered

NOTES

Structure

mnemonic

device

✓

Recall:

Absorb

UV light

max

Extinction

coefficient

(x10

-3

)

259 0.7

278 1.1

279 5.2

PTT family

(push-to-talk)

360 nm

Amino&Acids:&Classification

• The 20 amino acids found in proteins can be

placed in five families based on the physical and

chemical properties of their R groups:

• Hydrophobic, aliphatic (6)

• Hydrophobic, aromatic (3)

• Special (hydrophobic/hydrophilic)(2)

• Hydrophilic, polar (4)

• Hydrophilic, charged (5)

PTT family

Gavlip family

Amino&Acids:&Classification

Special (Sulfur)

Methionine Met M 1922 2

Ala+Me/ether

Cysteine Cys C 1899 2

Most like straight-chain aliphatic

Ala+SH (thiol)

Name 3-letter

1-letter

abundance

in proteins

Year

discovered

NOTES

Structure

mnemonic

device

can ionize; nucleophile 10.5

Hydropathy

index (

Ile 4.5

Val 4.2

Leu 3.8

Phe 2.8

Tyr –1.3

Met 1.9

Cys 2.5

• Cysteine can form disulfide bonds:

–S–S–R

⇌ R

–SH + R

–SH

Oxidized Reduced

Cystine (1810) Cysteine

• Cysteine can ionize:

Cys–SH ⇌ Cys–S

–

(thiolate anion) + H

✓

Hydrophobic

/Hydrophilic (Cys)

Amino&Acids:&Classification

Special (Sulfur)

Methionine Met M 1922 2

Ala+Me/ether

Cysteine Cys C 1899 2

Most like straight-chain aliphatic

Ala+SH

Name 3-letter

1-letter

abundance

in proteins

Year

discovered

NOTES

Structure

mnemonic

device

can ionize; nucleophile 10.5

• Cysteine can form disulfide bonds:

–S–S–R

⇌ R

–SH + R

–SH

Oxidized Reduced

Cystine (1810) Cysteine

• Cysteine can ionize:

Cys–SH ⇌ Cys–S

–

(thiolate anion) + H

✓

MC family

(master of ceremony)

Hydrophobic

/Hydrophilic (Cys)

Amino&Acids:&Classification

• The 20 amino acids found in proteins can be

placed in five families based on the physical and

chemical properties of their R groups:

• Hydrophobic, aliphatic (6)

• Hydrophobic, aromatic (3)

• Special (hydrophobic/hydrophilic)(2)

• Hydrophilic, polar (4)

• Hydrophilic, charged (5)

PTT family

Gavlip family

MC family

Amino&Acids:&Classification

Hydrophilic, polar

Glutamine Gln Q 1883

Glx; gets hydrolyzed to Glu

Amide of Glu

Asparagine Asn N 1806 4

First isolated from asparagus

Asx; gets hydrolyzed to Asp

Amide of Asp

Serine Ser S 1865 7

Isolated from Sericin, polar

cousin of Ala

hydroxyl+Ala

Name 3-letter

1-letter

abundance

in proteins

Year

discovered

NOTES

Structure

mnemonic

device

Threonine Thr T 1935 6

Me+Ser

✓

Gln Asn

Ser Thr

Two chiral centers (L & D)

Amino&Acids:&Classification

Hydrophilic, polar

Qnst family

Glutamine Gln Q 1883 4

Amide of Glu

Asparagine Asn N 1806 4

Amide of Asp

Serine Ser S 1865 7

hydroxyl+Ala

Name 3-letter

1-letter

abundance

in proteins

Year

discovered

NOTES

Structure

mnemonic

device

Threonine Thr T 1935 6

Me+Ser

✓

Gln Asn

Ser Thr

These amino acids side chains can form hydrogen

bonds.

Glx; gets hydrolyzed to Glu

First isolated from asparagus

Asx; gets hydrolyzed to Asp

Isolated from Sericin, polar

cousin of Ala

Two chiral centers (L & D)

Amides

Alcohols