Open AccessSmall Peptides for Inhibiting Serum Amyloid A Aggregation
Author(s) -
Asis K. Jana,
Augustus B Greenwood,
Ulrich H. E. Hansmann
Publication year - 2021
Publication title -
acs medicinal chemistry letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 66
ISSN - 1948-5875
DOI - 10.1021/acsmedchemlett.1c00456
Subject(s) - peptide , amyloidosis , serum amyloid a , amyloid (mycology) , amino acid , amyloid fibril , peptide sequence , chemistry , drug , inflammation , serum amyloid a protein , sequence (biology) , pharmacology , biochemistry , medicine , immunology , disease , pathology , amyloid β , gene
Deposition of human serum amyloid A (SAA) amyloids in blood vessels, causing inflammation, thrombosis, and eventually organ damage, is commonly seen as a consequence of certain cancers and inflammatory diseases and may also be a risk after SARS-COV-2 infections. Several attempts have been made to develop peptide-based drugs that inhibit or at least slow down SAA amyloidosis. We use extensive all-atom molecular dynamic simulations to compare three of these drug candidates for their ability to destabilize SAA fibrils and to propose for the best candidate, the N-terminal sequence SAA1-5, a mechanism for inhibition. As the lifetime of peptide drugs can be increased by replacing l-amino acids with their mirror d-amino acids, we have also studied corresponding d-peptides. We find that DRI-SAA1-5, formed of d-amino acids with the sequence of the peptide reversed, has similar inhibitory properties compared to the original l-peptide and therefore may be a promising candidate for drugs targeting SAA amyloidosis.