PREPARATIONS OF PSI-PEPTIDE BOND AND PEPTIDE-ALDEHYDE INHIBITORS OF ATRIAL GRANULE SERINE PROTEINASE, A CANDIDATE PROCESSING ENZYME OF PROATRIAL NATRIURETIC FACTOR

被引:4
作者
DAMODARAN, A [1 ]
HARRIS, RB [1 ]
机构
[1] VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT BIOCHEM & MOLEC BIOPHYS,RICHMOND,VA 23298
来源
JOURNAL OF PROTEIN CHEMISTRY | 1995年 / 14卷 / 06期
关键词
ANF; ATRIAL NATRIURETIC FACTORS; ATRIAL GRANULE SERINE PROTEINASE; PEPTIDE INHIBITORS; PEPTIDE ALDEHYDES; PROCESSING ENZYMES; PSEUDO-BOND INHIBITORS; SERINE PROTEINASE; SWERN OXIDATION;
D O I
10.1007/BF01888137
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Pseudo-peptide bond inhibitors (Psi-bond inhibitors) and peptide-aldehyde inhibitors of atrial granule serine proteinase, the candidate processing enzyme of pro-atrial natrieuretic factor, are prepared in high yield and purity by novel synthetic routes, The Psi-bond compounds retain essential residues for enzyme binding, but place the enzyme inhibition site in the midst of the peptide sequence. Thus, Bz-APR-Psi-LR and Bz-APR-Psi-SLRR can be considered ''readthrough inhibitors'' of atrial granule serine proteinase. The most potent Psi-peptide, Bz-APR-Psi-SLRR (IC50 = 250 mu M), is about fivefold less potent than the best peptide-aldehyde inhibitor (EACA-APR-CHO), and both the Psi-bond and peptide-aldehyde compounds are competitive, reversible inhibitors of the enzyme. The Psi-bond peptides containing two C-terminal Arg residues are three- to tenfold more potent than the analogous compounds containing only one C-terminal Arg residue, confirming the importance of both Arg residues in the enzyme processing recognition site. As expected, because of their moderate potencies, the Psi-peptides are not useful affinity ligands for purification of atrial granule serine proteinase, but both peptide aldehydes are effective affinity ligands [Damodaran and Harris (1995), J. Protein Chem., this issue].
引用
收藏
页码:431 / 440
页数:10
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