Carbonyl-17O n.m.r. of amino acid and peptide carboxamide and methyl ester derivatives§

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Abstract
Specific carbonyl enrichment with 17O of amino acid OMe esters by up to 103 times over natural abundance was affected by treated [17O]-.alpha.-COOH amino acids with SOCl2 in MeOH. Carbonyl-[17O]-Gly-NH2, Gly-NHCH3 and Gly-N(CH3)2 were obtained from [17O]-Gly-OMe by (methyl)aminolysis with NH3, CH3NH2 and (CH3)2NH gases, respectively. Peptide [17O]-carboxamides were prepared by (methyl)aminolysis of Z-Pro-Leu-[17O]-Gly-OMe [Z = benzyloxycarbonyl] followed by catalytic hydrogenation to remove the Z group. 17O chemical shifts of amino acid and peptide carboxamides in H2O, MeOH, CH3CN and DMSO [dimethyl sulfoxide] were 260-324 ppm. downfield relative to H2O, depending on .alpha.-NH2 ionization, substitution on both amino groups and solvent H bonding, primarily to amide oxygen. Introduction of an amide-N methyl group usually caused upfield shifts (.apprx. - 10 ppm.), attributed to elimination of one NH bond, while a second N methylation had the opposite effect. Amino acid and peptide OMe ester carbonyl-[17O] resonances appeared 326-359 ppm. downfield relative to H2 reflecting on side chain interactions, state of .alpha.-NH2 ionization and H-bonding with the solvent. Effective rotational correlation times for glycine and peptide carboxamide-[17O], calculated from T2 relaxation data, were of similar magnitude to values derived from solution properties and depended on the MW and solvent viscosity.