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.
Acher
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Laboratory of Pharmacological and Toxicological Chemistry and Biochemistry, URA 400 CNRS, University René Descartes, Paris, France.
Azerad
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R
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