CM'224' 'rganic'chemistry'ii Spring'2013,'Des'Plaines' 'Prof.'Chad'Landrie 2 3 N cysteine (Cys) S oxidation S S 3 N cystine N 3 Lecture'18:'April'2,'2013 Disaccharides+&+Polysaccharides Amino+acids++(26.1926.3)
Alkyla&on)Gives)Glycosides glycoside: carbohydrate derivative where hydroxyl group has been replaced by another group (e.g., methoxy). glucoside: glycoside of glucose or methyl 2,3,4,6-tetra-methyl-α-glucopyranoside similar to Williamson ether synthesis, but no strong base (degrade carbos) retention of configuration at anomeric carbon under basic cond. rganic Chemistry II (CM 224) Slide 2
Alkyla&on)Gives)Glycosides Board Work: Mechanism reversible reaction = thermodynamic product is major carbocation intermediate = only anomeric is substituted cite alkyl group first; replace -ose with -oside for glycosides rganic Chemistry II (CM 224) Slide 3
Dissaccharides 1 4-α-glycoside anomer of glycosyl donor carbon locant with - group anomeric carbon of glycosyl donor from hydrolysis of starch hemiacetal in right-hand unit = in equilib with aldehyde form = reducing sugar exibits mutarotation since glucose unit on the right is hemiacetal rganic Chemistry II (CM 224) Slide 4
Dissaccharides 1 4-β-glycoside anomer of glycosyl donor carbon locant with - group anomeric carbon of glycosyl donor from hydrolysis of cellulose hemiacetal in right-hand unit = in equilib with aldehyde form = reducing sugar exibits mutarotation since glucose unit on the right is hemiacetal rganic Chemistry II (CM 224) Slide 5
Dissaccharides 1 4-β-glycoside anomer of glycosyl donor carbon locant with - group anomeric carbon of glycosyl donor human & cow s milk sugar hemiacetal in right-hand unit = in equilib with aldehyde form = reducing sugar exibits mutarotation since glucose unit on the right is hemiacetal rganic Chemistry II (CM 224) Slide 6
Reducing)Dissacharides Disaccharides with a monomer that contains a hemiacetal are reducing sugars and exhibit mutarotation CuS 4 Glu C 2 + Cu 2 (s) rganic Chemistry II (CM 224) Slide 7
Non8Reducing)Dissacharides Sucrose is a 1 2-glycoside; α or β is not specified since each monomer is a glycoside with α/β anomers two different sugar monomers no hemiacetal = not reducing sugar does not exibit mutarotation since fructose unit on the right is acetal, not hemiacetal rganic Chemistry II (CM 224) Slide 8
Polysaccharides all β-1 4 linkages component of plant cell walls poorly digested by humans source of dietary fiber purest form in cotton rganic Chemistry II (CM 224) Slide 9
Polysaccharides all α-1 4 linkages one component of starch (20%) energy source: metabolized to glucose rganic Chemistry II (CM 224) Slide 10
Polysaccharides α-1 4 linkages α-1 6 branches 2nd component of starch (80%) rganic Chemistry II (CM 224) Slide 11
Sugar)Subs&tutes Splenda (sucralose) makers sued for: Made from sugar, so it tastes like sugar. rganic Chemistry II (CM 224) Slide 12
CM'224' 'rganic'chemistry'ii Spring'2013,'Des'Plaines' 'Prof.'Chad'Landrie Ch.'26:'Amino'Acids,'PepIdes'and' Proteins Amino+Acids:+26.1926.3
CM'224' 'rganic'chemistry'ii Spring'2013,'Des'Plaines' 'Prof.'Chad'Landrie ClassificaIon'and'Structure Sec>on+26.1
Amino)Acids Amino acids contain an amino group and a carboxylic acid. At physiological p, zwitterion is major form. 2 N 3 N R R uncharged: neutral zwitterion: neutral What is the most stable neutral form of amino acids? rganic Chemistry II (CM 224) Slide 15
Amino)Acids Amino acids contain an amino group and a carboxylic acid. At physiological p, zwitterion is major form. 2 N 3 N R R uncharged: neutral zwitterion: neutral high melting points (decompose before melting) soluble in water not soluble in nonpolar solvents rganic Chemistry II (CM 224) Slide 16
Amino)Acid)Classifica&on α N 3 C an α-amino acids used in biosynthesis of ethylene 3 N β α C a β-amino acid part of coenzyme A (CoA) 3 N γ β α C a γ-amino acid (GABA) transmission of nerve impulses rganic Chemistry II (CM 224) Slide 17
Amino)Acid)Classifica&on > 700 naturally occurring L-α-amino acids monomers of proteins (20) essential = not produced in the body; must consume peptide bonds formed by condensation of α-amino acids rganic Chemistry II (CM 224) Slide 18
Amino)Acid)Classifica&on > 700 naturally occurring L-α-amino acids monomers of proteins (20) essential = not produced in the body; must consume peptide bonds formed by condensation of α-amino acids rganic Chemistry II (CM 224) Slide 19
Amino)Acid)Classifica&on > 700 naturally occurring L-α-amino acids monomers of proteins (20) essential = not produced in the body; must consume peptide bonds formed by condensation of α-amino acids rganic Chemistry II (CM 224) Slide 20
Amino)Acid)Side8Chain Primary Difference between side-chains: 1. Size and Shape 2. Electronic characteristics L-Amino acids can be categorized by the electronic nature of their side chains: 1. Nonpolar (neutral) 2. Polar (neutral) 3. Acidic (anionic) 4. Basic (cationic) rganic Chemistry II (CM 224) Slide 21
Amino)Acid)Classifica&on 1. Nonpolar Side-chains 3 N smallest only achiral amino acid no side-chain adds length and flexibility to peptides & proteins glycine (Gly) rganic Chemistry II (CM 224) Slide 22
Amino)Acid)Classifica&on 1. Nonpolar Side-chains 3 N C 3 3 N alanine (Ala) 3 N valine (Val) 3 N electronically similar hydrophobic side-chains size: Gly < Ala < Val < Leu Ile most sperical (largest) leucine (Leu) isoleucine (Ile) rganic Chemistry II (CM 224) Slide 23
Amino)Acid)Classifica&on 1. Nonpolar Side-chains 3 N SC 3 S atom increases polarizability (little increase in polarity) increased dispersion forces methionine (Met) rganic Chemistry II (CM 224) Slide 24
Amino)Acid)Classifica&on 2 N proline (Pro) 1. Nonpolar Side-chains N N 3 only cyclic amino acid relatively compact (few rotatable bonds) no N- bonds in a peptide = no -bonding large effect on shape of proteins Pro-Gly rganic Chemistry II (CM 224) Slide 25
Amino)Acid)Classifica&on 1. Nonpolar Side-chains 3 N phenylalanine (Phe) 3 N N tryptophan (Trp) aromatic side-chains large and hydrophobic Trp is larger and more electron-rich (EDG N) and is more polarizable Trp specialized & less abundant in proteins rganic Chemistry II (CM 224) Slide 26
Amino)Acid)Classifica&on 1. Nonpolar Side-chains 3 N phenylalanine (Phe) 3 N N tryptophan (Trp) aromatic side-chains large and hydrophobic Trp is larger and more electron-rich (EDG N) and is more polarizable Trp specialized & less abundant in proteins rganic Chemistry II (CM 224) Slide 27
Amino)Acid)Classifica&on 2. Polar, But Nonionized Side-Chains 3 N serine (Ser) 3 N Threonine (Thr) ydroxyl side-chains -bonding Ser smallest (~Ala) and typically exposed to water Thr sterically hindered - group; less -bonding rganic Chemistry II (CM 224) Slide 28
Amino)Acid)Classifica&on 2. Polar, But Nonionized Side-Chains 3 N Tyrosine (Tyr) phenolic side-chain similar to phenylalanine increased -bonding rganic Chemistry II (CM 224) Slide 29
Amino)Acid)Classifica&on 2. Polar, But Nonionized Side-Chains 2 3 N S oxidation cysteine (Cys) thiol side-chain; similar to serine can be oxidized to form covalent bonds (disulfide bonds) S S 3 N cystine N 3 rganic Chemistry II (CM 224) Slide 30
Amino)Acid)Classifica&on 2. Polar, But Nonionized Side-Chains 3 N 2 N asparagine (Asn) 3 N N 2 glutamine (Gln) terminal amide groups very polar; interact strongly with water by -bonding usually found in regions in contact with water rganic Chemistry II (CM 224) Slide 31
Amino)Acid)Classifica&on 3. Acidic Side-Chains 3 N aspartic acid (Asp) 3 N glutamic acid (Glu) almost completely deprotonated acid sidechain as physiological p 1º function is to ionically bond with cations like metals and ammonium ions rganic Chemistry II (CM 224) Slide 32
Amino)Acid)Classifica&on 4. Basic Side-Chains 3 N N 3 lysine (Lys) 3 N N C N 2 2 N arginine (Arg) 3 N N N histidine (is) contain nitrogen atoms form ionic bonds to anions like phosphate histidine ~ 50% protonated at physiological p is involved in transporting protons from one site to another; can form complexes to metals rganic Chemistry II (CM 224) Slide 33
Amino)Acid)Classifica&on 4. Basic Side-Chains contain nitrogen atoms form ionic bonds to anions like phosphate histidine ~ 50% protonated at physiological p is involved in transporting protons from one site to another; can form complexes to metals rganic Chemistry II (CM 224) Slide 34
Interac&ons)Between)Amino)Acids 3 N S S N 3 1. Disulfide Bridge: Between two cysteines. Strongest intermolecular VWF; covalent N 2 N 2 N N N 2. Salt bridge: electrostatic attraction between oppositely charged ions N N N 3. -bond: postively polarized or N bond interacts with EN atom (N or ; occassionally F) N 3 C C 3 N 4. LDFs: induced-dipole/induceddipole attractions between nonpolar polarizable groups rganic Chemistry II (CM 224) Slide 35
CM'224' 'rganic'chemistry'ii Spring'2013,'Des'Plaines' 'Prof.'Chad'Landrie Isoelectric'Points Sec>on+26.2
enderson8asselbach)equa&on What percentage of each form exists in a 1.0 M solution buffered at a p of 9.00? [A] = 83% [A ] = 17% [A ] = 0.20[A] rganic Chemistry II (CM 224) At a p of 9.0, none of the fully protonated form will exist. Therefore, only pka2 is relevant. Use the pka closest to p of soln [A ] + [A] = 1.00 M 0.20[A] + [A] = 1.00 M 1.2[A] = 1.00 M [A] = 83% Slide 37
Titra&on)of)Amino)Acid 3 N fully protonated net charge = +1 3 N only amine protonated net charge = 0 rganic Chemistry II (CM 224) 2 N fully deprotonated net charge = 1 Slide 38
Isoelectric)Point The isoelectric point (pi) is the p at which an amino acid exists as its zwitterion and is neutral. The pi is the average of the two pkas that involve the neutral zwitterion. average two lowest pkas average two pkas average two highest pkas rganic Chemistry II (CM 224) Slide 39
Isoelectric)Point The isoelectric point (pi) is the p at which an amino acid exists as its zwitterion and is neutral. The pi is the average of the two pkas that involve the neutral zwitterion. At p = 2.77 N 3 average two lowest pkas rganic Chemistry II (CM 224) Slide 40
Isoelectric)Point)of)Proteins Proteins also have an overall isoelectric point (pi). Solubilities and properties strongly affected by p of medium. Solubility lowest at pi since net charge is zero. rganic Chemistry II (CM 224) Slide 41
Gel8Electrophoresis anionic proteins migrate toward cathode (+/ve) and vice versa larger protein charge (electrostatic force) = faster migration larger protein size (friction force) = slower migration rganic Chemistry II (CM 224) Slide 42
CM'224' 'rganic'chemistry'ii Spring'2013,'Des'Plaines' 'Prof.'Chad'Landrie Synthesis'of'Amino'Acids Sec>on+26.3
Synthesis)of)Amino)Acids 1. ell-volhard-zelinski Reaction proceeds through acyl bromide enol gives racemic mixture since enol is planar rganic Chemistry II (CM 224) Slide 44
Synthesis)of)Amino)Acids 2. Reductive Amination of α-ketoacids proceeds through imine intermediate reduced by NaB4 or NaCNB4 or 2/Pd rganic Chemistry II (CM 224) Slide 45
Synthesis)of)Amino)Acids 3. Strecker Synthesis board work proceeds through imine intermediate cyanide adds to imine rganic Chemistry II (CM 224) Slide 46
Synthesis)of)Amino)Acids 4. Acetamidomalonate Synthesis Alalgous to malonate synthesis gives racemic product rganic Chemistry II (CM 224) Slide 47
CM'224' 'rganic'chemistry'ii Spring'2013,'Des'Plaines' 'Prof.'Chad'Landrie Next'Lecture.'.'. Ch.+26:+Proteins