title: HIV-1 capsid assembly inhibitor (CAI) peptide: structural preferences and delivery into human embryonic lung cells and lymphocytes.
abstract: The Human immunodeficiency virus 1 derived capsid assembly inhibitor peptide (HIV-1 CAI-peptide) is a promising lead candidate for anti-HIV drug development. Its drawback, however, is that it cannot permeate cells directly. Here we report the transport of the pharmacologically active CAI-peptide into human lymphocytes and Human Embryonic Lung cells (HEL) using the BioShuttle platform. Generally, the transfer of pharmacologically active substances across membranes, demonstrated by confocal laser scanning microscopy (CLSM), could lead to a loss of function by changing the molecule's structure. Molecular dynamics (MD) simulations and circular dichroism (CD) studies suggest that the CAI-peptide has an intrinsic capacity to form a helical structure, which seems to be critical for the pharmacological effect as revealed by intensive docking calculations and comparison with control peptides. This coupling of the CAI-peptide to a BioShuttle-molecule additionally improved its solubility. Under the conditions described, the HIV-1 CAI peptide was transported into living cells and could be localized in the vicinity of the mitochondria.
authors.affiliation: Division of Molecular Toxicology, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Braun
authors.forename: Martin
authors.initials: M
authors.lastname: Frank
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Pipkorn
authors.forename: Jennifer
authors.initials: J
authors.lastname: Reed
authors.forename: Herbert
authors.initials: H
authors.lastname: Spring
authors.forename: Jürgen
authors.initials: J
authors.lastname: Debus
authors.forename: Bernd
authors.initials: B
authors.lastname: Didinger
authors.forename: Claus-Wilhelm
authors.initials: CW
authors.lastname: von der Lieth
authors.forename: Manfred
authors.initials: M
authors.lastname: Wiessler
authors.forename: Waldemar
authors.initials: W
authors.lastname: Waldeck
mesh_terms: D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D002942:Circular Dichroism; D003198:Computer Simulation; D003593:Cytoplasm / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D016655:HIV Core Protein p24 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D006801:Humans; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000378:metabolism; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D017433:Protein Structure, Secondary; D012997:Solvents / Q000737:chemistry; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000737:chemistry; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000737:chemistry
chemical_list: D019380:Anti-HIV Agents; D016655:HIV Core Protein p24; D010446:Peptide Fragments; D010455:Peptides; D012997:Solvents; D054301:gag Gene Products, Human Immunodeficiency Virus; C514799:p24 protein, Human Immunodeficiency Virus Type 1; D054322:tat Gene Products, Human Immunodeficiency Virus; C422951:tat peptide (48-60), Human immunodeficiency virus 1