Active Site Mutations Change the Cleavage Specificity of Neprilysin

Neprilysin (NEP), a member of the M13 subgroup of the zinc-dependent endopeptidase family is a membrane bound peptidase capable of cleaving a variety of physiological peptides. We have generated a series of neprilysin variants containing mutations at either one of two active site residues, Phe563 and Ser546. Among the mutants studied in detail we observed changes in their activity towards leucine5-enkephalin, insulin B chain, and amyloid β1–40. For example, NEPF563I displayed an increase in preference towards cleaving leucine5-enkephalin relative to insulin B chain, while mutant NEPS546E was less discriminating than neprilysin. Mutants NEPF563L and NEPS546E exhibit different cleavage site preferences than neprilysin with insulin B chain and amyloid ß1–40 as substrates. These data indicate that it is possible to alter the cleavage site specificity of neprilysin opening the way for the development of substrate specific or substrate exclusive forms of the enzyme with enhanced therapeutic potential

Chemo-mechanical Caries Removal System- A Brief Review

Chemomechanical caries removal involves the chemicalsoftening of carious dentine followed by its removal by gentleexcavation. Since, its inception in 1980’s, CMCR has been originally marketed as 3 different systems, viz., Caridex, Carisolv® & Papacarie®. Caridex required large volumes of solution and a special applicator tip, which weaned its popularity around 1990’s and thus, was discontinued to be marketed. Carisolv® & Papacarie® were later introduced around 2000, which had overcome the limitations of Caridex and are being used amongst the Clinicians aware of this technique.&nbsp