A Phase Ib Vaccine Trial Evaluating the Safety and Immunogenicity of HIV Lipopeptides by Two Administration Routes (Intramuscular And Intradermal) in Healthy Adult Volunteers. ANRS VAC16 Trial

Intramuscular (IM) administration of HIV lipopeptide vaccines have been shown to be able to induce HIV-1-specific T cell-mediated immune responses. The objective of this trial was to evaluate the safety and immunogenicity of LIPO-4 vaccine (HIV lipopeptides including 4 peptides from Gag, Pol, RT and Nef HIV-1 proteins, each peptide linked to TT) intradermally (ID) compared to IM administration.

开始日期2004-07-01

申办/合作机构

National Agency for Research on AIDS and Viral Hepatitis

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280

项与 Lipopeptides LIPO-4(French National Agency for Research on AIDS and Viral Hepatitis) 相关的文献（医药）

2024-12-31·Journal of Enzyme Inhibition and Medicinal Chemistry

Bacillus lipopeptides inhibit lipase activity and promote 3T3-L1 preadipocyte differentiation

Article

作者: Xiao, Rongfeng ; Chen, Meichun ; Chen, Deju ; Wang, Jieping ; Zheng, Xuefang ; Liu, Bo

Bacillus lipopeptides have been reported to display anti-obesity effects. In the present study, Lipopeptides from Bacillus velezensis FJAT-45028 that consisted of iturin, fengycin and surfactin were reported. The lipopeptides exhibited a strong lipase inhibition activity in a concentration-dependent manner with a half maximal inhibitory concentration of 0.012 mg/mL, and the inhibition mechanism and type were reversible and competitive, respectively. Results of CCK8 assay showed that 3T3-L1 preadipocyte cells were completely viable under treatment of 0.050-0.2 mg/mL lipopeptides for 24 or 48 h. It was found that the lipopeptides could increase lipid droplets in the differentiated 3T3-L1 adipocytes in tested concentration and suppress the expression of peroxisome proliferator-activated receptor gamma (PPARγ). These results indicated the potential anti-obesity mechanism of the tested lipopeptides might be to inhibit lipase activity but not to suppress lipid accumulation in the adipocytes. Moreover, the lipopeptides could elevate glucose utilisation by 14.43%-33.81% in the differentiated 3T3-L1 adipocytes.

2024-12-01·Bioorganic Chemistry

Impact of lipidation site on the activity of α-helical antimicrobial peptides

Article

作者: Sikorska, Emilia ; Wardowska, Anna ; Małuch, Izabela ; Bauer, Marta ; Wyrzykowski, Dariusz ; Makowska, Marta

Antimicrobial peptides (AMPs) display advantages over traditional antibiotics due to their broad spectrum of activity against various pathogens, and may even overcome bacterial drug resistance. However, despite their potential therapeutic benefits, widespread application of AMPs is limited by their instability, sensitivity to high salt concentrations, toxicity, and immunogenicity. Lipidation is a promising strategy in overcoming these drawbacks and potential problems for drug candidates. While N-terminal lipidation is a well-studied form of acylation of biologically active peptides, fatty acylation of the lysine side chain has still been poorly explored. In this study, we examined systematic introduction of octanoic (C₈) or decanoic (C₁₀) acid into the sequences of three antimicrobial α-helical peptides, namely LL-I, LK6, and ATRA-1, by acylation of subsequent lysine residues, resulting in 17 lipopeptides. Fatty acid lengths optimal for antimicrobial activity were selected based on a previous study on the N-terminal lipidated counterparts of these peptides. Shuffling the position of the fatty acid tails in the sequences of the peptides preserved high activity against Gram-positive bacteria, increased activity against Gram-negative strains and reduced cytotoxicity, compared to the N-terminal acylated counterparts. In the case of the LL-I and LK6 conjugates, the interactions with artificial negatively charged membranes induced formation of an α-helical structure but without a direct correlation between helicity and amphipathicity. Unexpectedly, the ATRA-1 derivatives showed only a small tendency, if any, to adopt a helical structure upon binding to POPG vesicles, which may indicate a non-helical active conformation. A more detailed study of the selected analogues, namely LL-I-4C₈, LK6-7C₈, and ATRA-1-11C₁₀, provided evidence of a tendency to self-assemble into clumped and/or isolated fibrils, micelles or clusters of micelles, and proved that the lipid bilayer is the main target of action of the tested lipopeptides. In summary, the results of the present study highlight that alternative conjugation sites for lipid modification of AMPs, rather than the commonly applied N-terminal conjugation site, may improve the selectivity of action and be feasible in testing for the development of new lipid-peptide conjugates.

2024-11-06·Journal of the American Chemical Society

Lipidation Engineering in Daptomycin Biosynthesis

Article

作者: Kang, Hahk-Soo ; Park, Sehong ; Je, Hyun-Woo ; Ji, Chang-Hun ; Lee, Kunwoo

Lipopeptides are an important family of natural products, some of which are clinically used as antibiotics to treat multidrug-resistant pathogens. Although the lipid moieties play a crucial role in balancing antibacterial activity and hemolytic toxicity, modifying the lipid moieties has been challenging due to the complexity of the lipidation process in lipopeptide biosynthesis. Here, we show that the lipid profile can be altered by engineering both secondary and primary metabolisms, using daptomycin as an example. First, swapping the fatty acyl AMP ligase (FAAL) gene dptF with foreign FAAL homologs improved the fatty acyl specificity of the lipidation process for decanoic acid. Then, the introduction of Mycobacterium type I fatty acid synthase operon (MvFAS-Ib/MvAcpS) and Cryptosporidium thioesterase (CpTEII) enriched the fatty acid pool with decanoic acid in Streptomyces roseosporus. The engineered fatty acid metabolism eliminates the need for external decanoic acid supplementation by enabling S. roseosporus to biosynthesize decanoic acid. By complete engineering of the lipidation process, we achieved, for the first time, high-purity, natural production of daptomycin. The lipidation engineering approach we demonstrate here lays the foundation for the lipidation control in lipopeptide biosynthesis.

项与 Lipopeptides LIPO-4(French National Agency for Research on AIDS and Viral Hepatitis) 相关的新闻（医药）

2023-02-14

·BioSpace

Thylacine Biotherapeutics Licenses Novel Antiviral Peptide Platform from Columbia University

NEW YORK, Feb. 14, 2023 /PRNewswire/ -- Thylacine Biotherapeutics Inc. ("Thylacine Bio"), a privately held biotech company dedicated to combating infectious disease, announced today it has entered into a license agreement with Columbia University ("Columbia") for worldwide exclusive rights to develop and commercialize a novel antiviral peptide platform. This new platform addresses pathogens within 8 RNA virus families identified as likely sources of the next pandemic. Leading virologists, Matteo Porotto, PhD and Anne Moscona, MD, President-Elect of the American Society for Virology, of Columbia's Center for Host Pathogen Interaction, invented and refined this antiviral platform. Through a mechanism of action known as fusion inhibition, Thylacine Bio's licensed peptides bind to a specific structure on a virus that is necessary for cell entry. As a result, the peptides prevent infection, maintain potency as a virus evolves, and offer broad spectrum protection. "We are thrilled to work with the world-class scientists of the Moscona-Porotto lab at Columbia University on this groundbreaking antiviral platform," said Elma Hawkins, PhD, Thylacine Bio's Executive Chair. Platform lipopeptides can be rapidly and reactively engineered to respond to an outbreak within days. Thylacine Bio's lead lipopeptide, THY-01, was identified by the inventors just two weeks after the COVID-19 genetic sequence became known. Other benefits of THY-01 include protection against upper respiratory infection and progression to severe disease, reduction of transmission, and self-administration by delivery via the respiratory tract. THY-01 also exhibits pan-coronavirus inhibition, with efficacy against SARS-CoV-2, MERS, SARS, and coronaviruses that cause the common cold. The Company is currently conducting pre-clinical studies in preparation for human trials. "Using this new fusion inhibition lipopeptide platform, we have the potential to address pathogens within 8 RNA virus families identified as likely sources of the next pandemic. The Company will aggressively pursue the development of a robust pipeline to address both commercial and biothreat indications," added Dr. Hawkins. About Thylacine Biotherapeutics, Inc. Thylacine Biotherapeutics is developing a rapid response, broad spectrum antiviral platform. Our novel lipopeptides are engineered to target the viruses most likely to cause pandemics; limiting transmission, preventing infection, and reducing illness. Thylacine Bio's lead candidate, THY-01, demonstrates strong in vivo efficacy and broad-spectrum protection against COVID-19 and other coronaviruses that cause disease in humans. A pipeline to address both commercial and biothreat indications is under development. Contact Thylacine Biotherapeutics, Inc. Daniel Graifman, President and Chief Operating Officer dgraifman@thylacine-bio.com

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