PROTECTION OF THE PEPTIDE-BOND AGAINST ALPHA-CHYMOTRYPSIN BY THE PRODRUG APPROACH

被引：5

作者：

KAHNS, AH ^{[1
]}

FRIIS, GJ ^{[1
]}

BUNDGAARD, H ^{[1
]}

机构：

[1] ROYAL DANISH SCH PHARM,DEPT PHARMACEUT CHEM,2 UNIV PK,DK-2100 COPENHAGEN,DENMARK

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1993年 / 3卷 / 05期

关键词：

D O I：

10.1016/S0960-894X(00)80671-X

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

N-Hydroxymethylation of the N-terminal peptide bond in N-acetyl-L-phenylalanine amides was found to protect the C-terminal amide bond against cleavage by alpha-chymotrypsin. The N-hydroxymethyl derivatives are readily bioreversible, undergoing spontaneous hydrolysis at physiological pH, and are thus promising prodrugs to overcome the enzymatic barrier to absorption of various peptides.

引用

页码：809 / 812

页数：4

共 6 条

[1]

BUNDGAARD H, 1992, ADV DRUG DELIVER REV, V8, P1, DOI 10.1016/0169-409X(92)90014-H

[2] PRODRUGS OF PEPTIDES .9. BIOREVERSIBLE N-ALPHA-HYDROXYALKYLATION OF THE PEPTIDE-BOND TO EFFECT PROTECTION AGAINST CARBOXYPEPTIDASE OR OTHER PROTEOLYTIC-ENZYMES [J].

BUNDGAARD, H ;

RASMUSSEN, GJ .

PHARMACEUTICAL RESEARCH, 1991, 8 (03) :313-322

[3]

FAUCHERE JL, 1986, ADV DRUG RES, V15, P29

[4] PEPTIDES AND RELATED DRUGS - A REVIEW OF THEIR ABSORPTION, METABOLISM, AND EXCRETION [J].

HUMPHREY, MJ ;

RINGROSE, PS .

DRUG METABOLISM REVIEWS, 1986, 17 (3-4) :283-310

[5] PRODRUGS OF PEPTIDES .13. STABILIZATION OF PEPTIDE AMIDES AGAINST ALPHA-CHYMOTRYPSIN BY THE PRODRUG APPROACH [J].

KAHNS, AH ;

BUNDGAARD, H .

PHARMACEUTICAL RESEARCH, 1991, 8 (12) :1533-1538

[6]

LEE VHL, 1990, ADV DRUG DELIV REV, V4, P171

← 1 →