Linked Life Data

3527255

Source:http://linkedlifedata.com/resource/pubmed/id/3527255

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
1986-10-15
pubmed:abstractText
We have synthesized peptidyl fluoromethyl ketones that are specific inhibitors of the serine proteases alpha-chymotrypsin and porcine pancreatic elastase. By analogy with the corresponding aldehydes it is assumed that the fluoromethyl ketones react with the gamma-OH group of the active site serine to form a stable hemiacetal [Lowe, G., & Nurse, D. (1977) J. Chem. Soc., Chem. Commun., 815; Chen, R., Gorenstein, D.G., Kennedy, W.P., Lowe, G., Nurse, D., & Schultz, R.M. (1979) Biochemistry 18, 921; Shah, D.O., Lai, K., & Gorenstein, D.G. (1984) J. Am. Chem. Soc. 106, 4272]. 19F NMR studies of the chymotrypsin-bound trifluoromethyl ketone inhibitors Ac-Leu-ambo-Phe-CF3 and Ac-ambo-Phe-CF3 clearly indicate that the carbonyl carbon is tetrahedral at the active site of the enzyme. The inhibitor is bound as either the stable hydrate or the hemiacetal, involving the active site serine. The effect of varying the number of amino acid residues in the peptidyl portion of the inhibitor and the number of fluorines in the fluoromethyl ketone moiety is examined. In the series of trifluoromethyl ketone elastase inhibitors, the lowering of Ki concomitant with the change from a dipeptide analogue to a tetrapeptide analogue (Ac-Pro-ambo-Ala-CF3, Ki = 3 X 10(-3) M; Ac-Ala-Ala-Pro-ambo-Ala-CF3, Ki = 0.34 X 10(-6) M) correlates well with the variation in V/K for hydrolysis of the corresponding amide substrates. This trend is indicative of the inhibitors acting as transition-state analogues [Bartlett, P.A., & Marlowe, C.K. (1983) Biochemistry 22, 4618; Thompson, R.C. (1973) Biochemistry 12, 47].(ABSTRACT TRUNCATED AT 250 WORDS)
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3760-7
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1986
pubmed:articleTitle
Inhibition of serine proteases by peptidyl fluoromethyl ketones.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't