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66 terms

Amino Acids, Peptides, and Proteins

Ch 25
STUDY
PLAY
Amino acids
contain both a carboxyl group and some class of amine (usually primary)
polypeptides
more than 50 amino acid bonds
proteins
biological polypeptides
proline
the only amino acid that's not primary; secondary
L geometry
what type of geometry are amino acids?
Glycein
the only amino acid with no stereogenic center
zwitter ions
amino acids exist as these at biological pH
minimum solubility
pH is adjusted so that an amino acid's carboxylate and ammonium ions are at exactly equal concentrations; uncharged overall; isoelectronic point
isoelectronic point
(pKa of conj. acid of zwitter ion + pKa of qwitter ion)/2
polar side groups
raise water solubility
nonpolar side groups
reduce water solubility
aromatic rings
large and hydrophobic
polar
amide functions polar or nonpolar?
acidic side chains
electron rich and can participate in ionic bonding to metal ions and N+ species
basic side chains
form ionic bonds to phosphate and the like
HVZ
1. treat a carboxylic acid with P and Bromine, then
2. nucleophilic substitution in which ammonia reacts with an a-halo carboxylic acid to form an amino acid
amino acid synthesis
HVZ
strecker synthesis
combines three reactions in two steps: cyanohydrin formation followed by immediate alcohol to amine conversion, then hydrolysis
strecker synthesis
converts an aldehyde into an amino acid with the amine group on the former carbonyl carbon and a new carbon at the carboxyl position
racemic products
HVZ, strecker synthesis, diethylacetamidomalonate reagent
diethylacetamidomalonate
most versatile reaction; modified form of malonic ester synthesis
diethylacetamidomalonate reagent
1. treated with the ethoxide ion to form malonate's enolate ion
2. this is used to displace Cl or Br from an alkyl or benzyl halide
3. aqueous acid hydrolysis removes both the amide group and the ester alkoxy groups, allowing decarboxylation to the amino acid
hyrdolysis
HX, H2O, heat
amino acid reactions
acylation, ester formation, biochemical reactions
acylation
typical of the amino group; when treated with acid anhydride or acyl chloride, it converts to its amide
ester formation
typical of carboxyl group; treating the amino acid with the desired alcohol using dry HCl as a catalyst
ninhydrin reaction
yields a pink/purple adduct with an intense color
pyridoxal 5'-phosphate
PLP; active form of Vit B6; coenzyme
biochemical reactions
decarboxylation, transamination, tryosine derivations, enzymatic oxidation and hydrolysis
decarboxylation
results in CO2 and an amine; PLP is used
transamination
uses glutamate to make other amino acids
glutamate
biosynthesized by adding ammonia to a-ketoglutaric acid
catecholamines
dopamine, norepinephrine, and epinephrine; result from a conversion from tyrosine
enzymatic oxidation
treat an amino acid with
1. O2, enz.
2. enz.
PKU
results from incomplete breakdown of amino acids resulting in oxygenated products of ammonia, which is tied up as urea; lack phenylalanine hydroxylase
acid-catalyzed hydrolysis of amide bonds
first step of analysis; done with 6M HCl for 24hrs
Sanger's reagent
1-fluoro-2,4-dinitrobenzene; labels the N-terminus
dansyl chloride
5-(dimethylamino)naphthalene-1-sulfonyl chloride; also labels N-terminus
Edman degradation
uses phenylisothiocyanate
phenylisothiocyanate
removes one amino acid at a time, allowing successive identification of each amino acid from the N-terminus inward; phenyl-N=C=S; C=S acts as an internal nucleophile
carboxypeptidases
used for end-group analysis from the C-terminus; cleave just the C-terminus amino acid, so observation of which amino acids are freed in sequence can indicate the primary structure
selective hydrolysis
key is to use enzymes that hydrolyze only specific amino acids' bonds
MALDI
vaporizes peptides that lack sufficient volatility to be vaporized for analysis by conventional MS
conjugate acid
the species analyzed in MALDI
liposomes
drug delivery importance
approaches to peptide synthesis
solution phase and solid phase
amide
amino group protection results in? and uses benzyloxycarbonyl (Cbz or Z) and tert-butoxycarbonyl (Boc) and 9-fluorenylmethoxycarbonyl (FMOC) groups
Boc
removed by HBr only
Cbz
removed by HBr and hydrogenolysis
FMOC
removed by base treatment
deprotection
can't use hydrolysis (would hydrolyze amide bonds too)
1. HBr in acetic acid
2. hydrogenolysis in palladium
3. basic conditions, NH3
esters
carboxyl groups are protected as?
deprotection
methyl and ethyl esters are removed by dilute base, while benzyl esters can be removed by hydrogenolysis
DCCI
reagent used to couple the protected amino acids; yields dicyclohexylurea as it combines with the water released by peptide bond formation
DCCI
soluble in same solvent as the product
EDCI
it and its urea are soluble in water and can be easily separated; can be used in organic solvents
solid-phase peptide synthesis
an insoluble polymer support is used as the protecting group for the C-terminus. Boc-protected amino acids are coupled in sequence using DCCI, deptrotected, washed, and then coupled, deptrotected, etc.
once complete, the peptide can by removed by HBr in CF3COOH. THIS CAN BE AUTOMATED
secondary structure
alpha helix and beta pleated sheet
tertiary structure
folding or twisting; globular and fibrous
globular
enzymes, hydrophobic effect
hydrophobic effect
when placed in water, nonpolar amino acid side chains cause water molecules to become more ordered causing the protein to adopt a spherical shape which puts nonpolar inside
fibrous
keratins and collagen
coenzyme
organic and not covalently bonded to the enzyme
prosthetic
organic and are covalently bonded to the enzyme
quaternary structure
two or more peptide chains linked by non-peptide bonds; hemoglobin and insulin
GCPR
Guanine-coupled protein receptors; transmembrane proteins that sense the presence of some extracellular species and triggers a cellular respons