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Biomedical subjects

J Pluscec

Publications and source records attributed to J Pluscec.

At least 19 recordsLinked to original sources
PubMed1991

Phosphorus-containing inhibitors of HMG-CoA reductase. 2. Synthesis and biological activities of a series of substituted pyridines containing a hydroxyphosphinyl moiety.

A series of 2,3,4,(5),6-substituted pyridines containing a hydroxyphosphinyl functionally have been prepared and were evaluated for their ability to inhibit the enzyme HMG-CoA reductase. Systematic substitution of both R1-R4 and X-Y led to compounds of type 3-6 with in vitro potency greater than that of mevinolin (Na salt).

Animals↗
PubMed1988

Ketomethylureas. A new class of angiotensin converting enzyme inhibitors.

The design rationale for a new series of tripeptide derived angiotensin converting enzyme (ACE) inhibitors, which we term "ketomethylureas", is described. Analogs of tripeptide substrates (i.e. N-benzoyl-Phe-Ala-Pro) in which the nitrogen atom of the scissile amide bond and the adjacent asymmetric carbon atom of the penultimate amino acid residue are formally transposed give rise to this novel class of inhibitors. The most potent ketomethylureas inhibit ACE with I50 values in the nM range.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1985

Design of peptide derived amino alcohols as transition-state analog inhibitors of angiotensin converting enzyme.

A new amino alcohol modification designed to mimic the putative transition-state of amide bond cleavage by proteolytic enzymes has been incorporated into the scissile bond position of N-benzoyl-Phe-Ala-Pro, a known substrate of angiotensin converting enzyme (ACE). The resulting modified tripeptides (i.e. 4) are shown to be a new class of potent inhibitors of converting enzyme.

Amino Alcohols↗
PubMed1984

Design of conformationally constrained angiotensin-converting enzyme inhibitors.

Modification of alanyl proline by introduction of both zinc coordinating and S1 subsite binding interactions affords potent new carboxy- and mercapto-acyl dipeptide angiotensin-converting enzyme (ACE) inhibitors. Design of these inhibitors was guided by an extension of the hypothetical ACE active site model originally used to derive captopril. Significant increases in ACE inhibitory activity were observed by introduction of conformation constraint into acyclic acyl dipeptides, thus further defining the three dimensional structure of the ACE active site.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1984

Ketomethyldipeptides I. A new class of angiotensin converting enzyme inhibitors.

The design rationale for a new series of angiotensin-converting enzyme (ACE) inhibitors which incorporate a ketone substituent into a peptide backbone is described. Molecular regions which were expected to mimic the binding of an N-acyl tripeptide substrate at secondary binding sites S1 and S1' were systematically varied in order to study the specificity of inhibitor binding and optimize inhibition against ACE. The most effective ketomethyldipeptides inhibit ACE in the 10(-9) M range.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1984

Ketomethyldipeptides II. Effect of modifications of the alpha-aminoketone portion on inhibition of angiotensin converting enzyme.

Results of an investigation aimed at identifying the consequences of chemical modifications of the alpha-aminoketone moiety of ketomethyldipeptides on angiotensin converting enzyme (ACE) inhibition are reported. These studies lead to the conclusion that within this series, the optimal structural backbone formulation for inhibition of ACE is represented by 1. Introduction of a Sar-Pro C-terminal dipeptide in this system, in contrast to other inhibitor classes, is compatible with potent inhibitory activity. Other structure-activity relationships for ketomethyldipeptides and related derivatives are presented, and speculations on possible modes of binding of these inhibitors to ACE, and on the question of ketone rehybridization are offered.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1984

Streptomyces R61 DD-carboxypeptidase: hydrolysis of X-D-alanyl-D-alanine peptides measured by a fluorometric assay.

A fluorometric procedure for measuring the activity of DD-carboxypeptidase is described. The method is based on the reaction of one of the products, D-alanine, with o-phthaldialdehyde to form a highly fluorescent adduct. The method has been applied in examining a series of X-D-alanyl-D-alanine peptides as substrates of the penicillin-sensitive DD-carboxypeptidase from Streptomyces R61. The effect of the third residue, X, on kinetic parameters and its implications on the steric analog model for penicillin action are also discussed.

Alanine↗
PubMed1977

Streptomyces laurentii, a new species producing thiostrepton.

The taxonomic description of Streptomyces laurentii, a new species related to but distinguishable from the S. fradiae group, is presented. This new species produces thiostrepton but bears no taxonomic relationship to the known producers of the antibiotic: S. azureus, S. hawaiiensis, and Streptomyces X-14b.

Anti-Bacterial Agents↗