Addition of thiols to the double bond of dipeptide C-terminal dehydroalanine as a source of new inhibitors of cathepsin C

Synthesis of Hybrid Tripeptide Peptidomimetics Containing Dehydroamino Acid and Aminophosphonic Acid in the Chain and Evaluation of Their Activity toward Cathepsin C

“…Obtained K M was close to the values of 2.3 mM and 2.28 mM reported by Lenartowicz et al and Drąg et al, respectively. [17,38] The purity of the enzyme was checked by electrophoresis.…”

“…These observations suggest, that dehydroamino acid residues are a useful tool allowing to change the peptide conformation, independently of the other constraints. The introduction of residues of dehydroamino acid into the bioactive peptide sequence has thus become a useful tool for studying the structure‐function relationship and providing new analogs of increased activity [16–18] …”

“…In the case of short peptides, containing Δ E Phe, more ordered conformations had been observed. Compounds containing free, the unblocked amino group appeared as moderate inhibitors of the cathepsin C, [21–17] whereas fully protected peptides acted as very weak inhibitors [22] …”

A novel approach for obtaining α,β-diaminophosphonates bearing structurally diverse side chains and their interactions with transition metal ions studied by ITC

“…20 From a synthetic point of view, the presence of a dehydroamino acid residue in a peptide structure affords access to late-stage diversication of biomolecules through their chemical transformations. 21 Although the chemistry of classic dehydroamino acid derivatives with nucleophiles, such as amines and thiols, is well known, [22][23][24][25][26][27][28][29][30][31] the reactivity of their phosphonate counterparts is hardly ever described. Thus, we decided to demonstrate the utility of this synthetic approach as a general reaction for the preparation of N 0 -substituted a,b-diaminoethylphosphonates.…”