Category: Background

  • Full-Atom Peptide Design based on Multi-modal Flow Matching

    License: CC BY 4.0 arXiv:2406.00735v1 [q-bio.BM] 02 Jun 2024 Jiahan LiChaoran ChengZuofan WuRuihan GuoShitong LuoZhizhou RenJian PengJianzhu Ma Abstract Peptides, short chains of amino acid residues, play a vital role in numerous biological processes by interacting with other target molecules, offering substantial potential in drug discovery. In this work, we present PepFlow, the first multi-modal deep…

  • PepFlow: direct conformational sampling from peptide energy landscapes through hypernetwork-conditioned diffusion

     View ORCID ProfileOsama Abdin,  View ORCID ProfilePhilip M. Kim doi: https://doi.org/10.1101/2023.06.25.546443 Now published in Nature Machine Intelligence doi: 10.1038/s42256-024-00860-4 00000041 Abstract Deep learning approaches have spurred substantial advances in the single-state prediction of biomolecular structures. The function of biomolecules is, however, dependent on the range of conformations they can assume. This is especially true for peptides, a highly flexible class of molecules…

  • Cyclopeptide Ligand Generation

    Cyclopeptides, with their diverse building blocks and intricate three-dimensional architectures, offer unique opportunities for targeting some of the most challenging biological interactions, such as protein-peptide interactions. As nature has not evolved a specific ligand for every conceivable target, leveraging both traditional and computational methodologies has become crucial in generating novel cyclopeptide ligands for various proteins.…

  • Cyclopeptide Chemical Synthesis

    Since Emil Fischer pioneered peptide synthesis in 1901, the techniques for synthesizing peptides have significantly advanced. Innovations such as solid-phase peptide synthesis (SPPS), various protection and deprotection strategies, efficient coupling agents, automation, and high-yielding cyclization methods have all contributed to today’s ability to produce peptides. The modular nature of peptides and the effective coupling of…

  • Cyclopeptides’ Membrane Permeability

    Peptides face an energy barrier when crossing the apolar region of a membrane due to the need for desolvation of their polar groups, such as the hydrogen (H)-bond donors found in peptide bonds. Nature has evolved a solution to this challenge through cyclization, which promotes the formation of intramolecular H-bonds within peptides. This process reduces…

  • Cyclic peptide drugs approved for clinical use in the last 30years

    Vosoritide 2021 XVoclosporin 2021Setmelanotide 2020Bremelanotide 2019 XLutetium (177Lu) dotatate 2017Glecaprevir 2017Plecanatide 2017Voxilaprevir 2017Grazoprevir 2016Paritaprevir 2014 XDalbavancin 2014Oritavancin 2014Pasireotide 2012Linaclotide 2012 XRomidepsin 2009 XTelavancin 2009Lanreotide 2007Anidulafungin 2006Micafungin 2005Pramlintide 2005 XZiconotide 2004 XDaptomycin 2003 XCaspofungin 2001 XAtosiban 2000Eptifibatide 1998 XCarbetocin 1997 X means No sequence or structure similarity to previously approved drug

  • Three example cyclopeptides show shape complementarity between peptide and target

     three of these approved drugs, the structures of the cyclic peptide bound to their targets were recently solved by X-ray diffraction or cryomicroscopy and they nicely show the perfect shape complementarity between peptide and target which is the basis for the good binding properties  eptifibatide: PDB 7THO,ziconotide: PDB 7MIX, bremelanotide: PDB 7F55

  • CycloPeptides from Nature

    Cyclopeptides play crucial roles in nature, serving important functions across various organisms. In plants, fungi, and bacteria, they often act as defense mechanisms, while in animals, they can function as hormone signals. Interestingly, cyclopeptides are more common in our everyday lives than many realize. For instance, microcystins, a group of cyclic peptides produced by cyanobacteria…

  • Cyclic Peptides for Drug Development

    Xinjian Ji, Alexander L. Nielsen, Christian Heinis First published: 23 October 2023 https://doi.org/10.1002/anie.202308251 1 IntroductionCyclic peptides are polypeptide chains composed of canonical and non-canonical amino acids that are connected at distant positions to form macrocyclic structures. A wide range of cyclic peptides with diverse shapes, sizes and chemical compositions were found in nature and showcase the enormous…

  • Cyclopeptide drugs

    Table 1. Cyclic peptide drugs approved from 2006-2014 by the FDA and/or EMA Approved Generic name Indication Mode of action MW (Da) Route of administration Company 2006 Anidulafungin Fungal infections Fungal 1,3-β-d-glucan synthase inhibitor 1140 IV infusion Vicuron/Pfizer 2007 Lanreotide Acromegaly, neuroendocrine tumors Growth hormone release inhibitor 1156 SC, IM Ipsen 2009 Telavancin Complicated skin and…