Rational Design of Stapled Antimicrobial Peptides to Enhance Stability and <i>In Vivo</i> Potency against Polymicrobial Sepsis
Jih‐Chao Yeh, Prakash Kishore Hazam, Chu-Yi Hsieh, Po-Hsien Hsu, Wen‐Chun Lin, Yun‐Ru Chen, Chao-Chin Li, Jyh‐Yih Chen
Abstract
studies, one dual stapled peptide out of the series of candidates (TP4-3: FIIXKKSXGLFKKKAGAXKKKXIKK) showed significant activity, low toxicity, and high stability (in 50% human serum). When tested in cecal ligation and puncture (CLP) mouse models of polymicrobial sepsis, TP4-3 improved survival (87.5% on day 7). Furthermore, TP4-3 enhanced the activity of meropenem against polymicrobial sepsis (100% survival on day 7) compared to meropenem alone (37.5% survival on day 7). Molecules such as TP4-3 may be well suited for a wide variety of clinical applications.
Topics & Concepts
PotencyIn vivoAntimicrobialIn vitroMicrobiologyBiologySepsisPeptidePharmacologyAntimicrobial peptidesToxicityChemistryMedicineImmunologyBiochemistryBiotechnologyInternal medicineAntimicrobial Peptides and ActivitiesImmune Response and InflammationNeuropeptides and Animal Physiology