The Outcomes of Decorated Prolines in the Discovery of Antimicrobial Peptides from Temporin‐L

Abstract

Previously, we identified a potent antimicrobial analogue of temporin L (TL), [Pro3]TL, in which glutamine at position 3 was substituted with proline. In this study, a series of analogues in which position 3 is substituted with non‐natural proline derivatives, was investigated for correlations between the conformational properties of the compounds and their antibacterial, cytotoxic, and hemolytic activities. Non‐natural proline analogues with substituents at position 4 of the pyrrolidine ring were considered. Structure–activity relationship (SAR) studies of these analogues were performed by means of antimicrobial and cytotoxicity assays along with circular dichroism (CD) and NMR spectroscopic analyses for selected compounds. The most promising peptides were additionally evaluated for their activity against some representative veterinary microbial strains to compare with those from human strains. We identified novel analogues with interesting properties that make them attractive lead compounds.

Novel Antimicrobial Peptide from Temporin L in The Treatment of Staphylococcus pseudintermedius and Malassezia pachydermatis in Polymicrobial Inter-Kingdom Infection

“…Two strains of S. pseudintermedius were characterized for their pattern of antibiotic susceptibility as previously reported [ 14 ]. MRSP resulted oxacillin resistant and MSSP oxacillin susceptible.…”

Novel temporin L antimicrobial peptides: promoting self-assembling by lipidic tags to tackle superbugs

“…Minimal inhibitory concentrations (MIC) of all the peptides were determined in Mueller–Hinton medium by the broth microdilution assay, following the procedure already described 22 , 34 . The compounds were added to bacterial suspension in each well yielding a final cell concentration of 1 × 10 6 CFU/ml and a final compound concentration ranging from 0.78 to 100 µM.…”

“…The samples were then centrifuged for 5 min at 900 × g . The amount of haemoglobin released in the supernatant by lysed red blood cells was measured at 415 nm using a microplate reader (Infinite M200; Tecan, Salzburg, Austria) and compared to the complete lysis (100%), obtained by suspending erythrocytes in distilled water 34 , 35 . The colorimetric MTT assay was carried out to measure cellular metabolic activity in terms of cell viability 33 , 36 .…”

“…of 0.5 (k ¼ 500 nm) in 0.9% (w/v) NaCl were incubated for 40 min at 37 C with four different concentrations (ranging from 3.12 to 25 mM) of peptides 1B, 3B, 2B and C. Controls were erythrocytes treated with vehicle (water). The samples were then centrifuged for 5 min at 900 Â g. The amount of haemoglobin released in the supernatant by lysed red blood cells was measured at 415 nm using a microplate reader (Infinite M200; Tecan, Salzburg, Austria) and compared to the complete lysis (100%), obtained by suspending erythrocytes in distilled water 34,35 . The colorimetric MTT assay was carried out to measure cellular metabolic activity in terms of cell viability 33,36 .…”

Nigritanine as a New Potential Antimicrobial Alkaloid for the Treatment of Staphylococcus aureus-Induced Infections

“…The treated samples were then centrifuged for 5 min at 900× g. The amount of hemoglobin released in the supernatant by lysed red blood cells was measured at 415 nm using a microplate reader (Infinite M200; Tecan, Salzburg, Austria). The complete lysis was obtained by suspending erythrocytes in distilled water according to [68,69,70].…”