Synthesis of diastereoisomeric peptides incorporating cycloglutamic acids. Substrate specificity of vitamin K-dependent carboxylation.
Tripeptides Boc-X-Glu-Val where X is alpha-methyl glutamic acid or various cyclic analogues of glutamic acid, such as 1-amino-1,3-dicarboxycyclohexane (cis or trans-CHGA) or -cyclopentane (cis or trans-CPGA) have been synthesized. Methods for the selective protection, activation, and coupling of such unnatural amino acids are described. The peptides, which are potential competitive inhibitors of the vitamin K-dependent carboxylation, have been preliminarily tested with the rat liver microsomal carboxylase and found to be effective substrates of the carboxylation reaction.
Laboratory of Pharmacological and Toxicological Chemistry and Biochemistry, URA 400 CNRS, University René Descartes, Paris, France.
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D000595:Amino Acid Sequence; D000818:Animals; D002262:Carboxy-Lyases / Q000378:metabolism*; D003509:Cyclohexanecarboxylic Acids / Q000737:chemistry*; D005971:Glutamates / Q000737:chemistry; D018698:Glutamic Acid; D008862:Microsomes, Liver / Q000201:enzymology; D008969:Molecular Sequence Data; D010456:Peptides, Cyclic / Q000737:chemistry; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism; D013379:Substrate Specificity; D014812:Vitamin K / Q000737:chemistry*
D003509:Cyclohexanecarboxylic Acids; D005971:Glutamates; D010456:Peptides, Cyclic; D014812:Vitamin K; C000528:cycloglutamate; D018698:Glutamic Acid; D002262:Carboxy-Lyases