Synthesis and enzymatic activation of N-[N α-(4-amino-4-deoxypteroyl)-N δ-hemiphthaloyl-l-ornithiny]-l-phenylalanine, a candidate for antibody-directed enzyme …

JE Wright, A Rosowsky

Index: Wright, Joel E; Rosowsky, Andre Bioorganic and Medicinal Chemistry, 2002 , vol. 10, # 3 p. 493 - 500

Full Text: HTML

Citation Number: 6

Abstract

N-[Nα-(4-Amino-4-deoxypteroyl)-Nδ-hemiphthaloyl-l-ornithinyl]-l-phenylalanine (1), a carboxypeptidase A (CPA) cleavable prodrug was synthesized for use in an antibody directed strategy to improve the therapeutic selectivity of Nα-(4-amino-4-deoxypteroyl)-Nδ- hemiphthaloyl-l-ornithine (2), an extremely potent nonpoly-glutamatable DHFR inhibitor which is also highly cytotoxic. Compound 1 was shown by HPLC analysis to give a> 99% ...