AUTHOR=Ahmad Baseer , Hanif Quratulain , Wei Xubiao , Zhang Lulu , Sabir Naveed , Li Zhongxuan , Cheng Junhao , Khan Shahzad Akbar , Basit Abdul , Shahid Muhammad , Rehman Amin ur , Si Dayong , Zhang Rijun TITLE=In vitro Impact of Yeast Expressed Hybrid Peptide CATH-2TP5 as a Prophylactic Measure Toward Sepsis and Inflammation JOURNAL=Frontiers in Bioengineering and Biotechnology VOLUME=Volume 8 - 2020 YEAR=2020 URL=https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2020.00454 DOI=10.3389/fbioe.2020.00454 ISSN=2296-4185 ABSTRACT=CATH-2TP5 is a linear cationic hybrid peptide, consequent from naturally occurring antimicrobial peptide (AMPs) Cathelicidin-2 (CATH-2) and Immunomodulatory peptide Thymopentin (TP5), having dynamic and potent anti-inflammatory potential without hemolytic activity. The biocompatible mechanism of CATH-2TP5 essentials to explore new methodologies in the direction of biomedical applications. In this retrospectively study, an antiendotoxin and anti-inflammatory hybrid peptide CATH-2TP5 was emulated into pPICZα-A and successfully expressed in Pichia pastoris (P. pastoris). The recombinant CATH-2TP5 was purified through the Ni-affinity column and Reversed-phase HPLC. The purified CATH-2TP5 peptide exhibited robust anti-endotoxin activity and significantly (p < 0.05) neutralized the effect of lipopolysaccharide (LPS). Furthermore, CATH-2TP reduced the LPS-induced cytotoxic effects in murine RAW264.7 macrophages and significantly (p < 0.05) diminished the nitric oxide secretion and pro-inflammatory cytokines including TNF-α, IL-6, IL-1β, as well. In addition, associated to control and parental peptide the number of apoptotic cells was contracted with the treatment of CATH-2TP5. Collectively, this study provides a platform to comprehend the molecular mechanism of the expression and improvement of CATH-2TP5 peptide which may act as a therapeutic drug at the mass level.