C-terminal peptide alcohol, acid and amide analogs of desulfato hirudin54-65 as antithrombin agents
Research article published in Thrombosis research (1989)
Abstract
Analogs of the antithrombin peptide hirudin54-65 with C-terminal modifications have been synthesized in order to examine the requirements for alpha-thrombin inhibition. The C-terminal residue, Gln65, could be replaced with L-amino acids or amino alcohols with neutral or charged hydrophilic side chains without greatly affecting the peptide's antithrombin potency as determined by inhibition of thrombin-induced clot formation in human plasma in vitro. Derivatives with D- or L-amino carboxamides at position 65 had significantly reduced potency, but still retained activity. Deletion of residue 65 with conversion of residue 64 to the amide or alcohol derivative resulted in a three-fold loss of potency. In addition to these results the solid-phase synthesis of peptide alcohols via direct displacement of p-nitrobenzhydrylideneisonitroso resin attached peptides with the desired C-terminal amino alcohol is reported.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
Analogs of the antithrombin peptide hirudin54-65 with C-terminal modifications have been synthesized in order to examine the requirements for alpha-thrombin inhibition.
Por qué esto importa para la hirudoterapia
This study synthesized C-terminal analogs of the antithrombin peptide hirudin54-65 with modifications at position 65 to examine the structural requirements for alpha-thrombin inhibition, measuring potency by inhibition of thrombin-induced clot formation in human plasma in vitro. Replacement of the C-terminal residue with L-amino acids or amino alcohols having neutral or charged hydrophilic side chains did not greatly affect antithrombin potency, whereas derivatives with D- or L-amino carboxamides at position 65 showed significantly reduced but retained activity; deletion of residue 65 produced a three-fold loss of potency. Because the abstract explicitly names hirudin54-65 as the parent peptide, the work has a defensible biochemical relevance to ASH's domain as a structure-activity study of a hirudin fragment. However, the abstract makes no mention of leeches, leech saliva, leech secretome, or hirudotherapy, and the study is purely in vitro.
Citación
C-terminal peptide alcohol, acid and amide analogs of desulfato hirudin54-65 as antithrombin agents
Krstenansky JL et al. · Thrombosis research, 1989
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Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: June 18, 2026