Noncoded amino acids in protein engineering: Structure-activity relationship studies of hirudin-thrombin interaction
Research article published in Biotechnology and applied biochemistry (2018)
Abstract
The advent of recombinant DNA technology allowed to site-specifically insert, delete, or mutate almost any amino acid in a given protein, significantly improving our knowledge of protein structure, stability, and function. Nevertheless, a quantitative description of the physical and chemical basis that makes a polypeptide chain to efficiently fold into a stable and functionally active conformation is still elusive. This mainly originates from the fact that nature combined, in a yet unknown manner, different properties (i.e., hydrophobicity, conformational propensity, polarizability, and hydrogen bonding capability) into the 20 standard natural amino acids, thus making difficult, if not impossible, to univocally relate the change in protein stability or function to the alteration of physicochemical properties caused by amino acid exchange(s). In this view, incorporation of noncoded amino acids with tailored side chains, allowing to finely tune the structure at a protein site, would facilitate to dissect the effects of a given mutation in terms of one or a few physicochemical properties, thus much expanding the scope of physical organic chemistry in the study of proteins. In this review, relevant applications from our laboratory will be presented on the use of noncoded amino acids in structure-activity relationships studies of hirudin binding to thrombin.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
Noncoded amino acids in protein engineering: Structure-activity relationship studies of hirudin-thrombin interaction.
Por qué esto importa para la hirudoterapia
This review discusses the use of noncoded amino acids with tailored side chains to dissect physicochemical contributions to protein stability and function, focusing on structure-activity relationship studies of hirudin binding to thrombin from the authors' laboratory. The approach is presented as a way to overcome limitations of natural amino-acid mutagenesis by more independently varying properties such as hydrophobicity, conformational propensity, polarizability, and hydrogen bonding. For ASH's domain, this is relevant only indirectly: the abstract examines the hirudin-thrombin interaction at a molecular/protein-engineering level but does not mention leeches, hirudotherapy, or the leech secretome. The abstract also reports no specific quantitative findings, so it should be treated as a methodological review rather than evidence of clinical or whole-organism relevance.
Citación
Noncoded amino acids in protein engineering: Structure-activity relationship studies of hirudin-thrombin interaction
De Filippis V et al. · Biotechnology and applied biochemistry, 2018
Contexto clínico relacionado
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Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: June 18, 2026