Design of a specific peptide against phenolic glycolipid-1 from Mycobacterium leprae and its implications in leprosy bacilli entry
Document title: Design of a specific peptide against phenolic glycolipid-1 from Mycobacterium leprae and its implications in leprosy bacilli entry
Journal: Memorias do Instituto Oswaldo Cruz
Database: PERIÓDICA
System number: 000452399
ISSN: 0074-0276
Authors: 1
2
3
1
Institutions: 1Hospital Universitario, Centro Dermatológico Federico Lleras Acosta, Bogotá. Colombia
2Universidad de los Andes, Departamento de Química, Bogotá. Colombia
3Universidad del Quindío, Facultad de Ciencias de la Salud, Armenia, Quindío. Colombia
Year:
Volumen: 117
Country: Brasil
Language: Inglés
Document type: Artículo
Approach: Experimental, aplicado
English abstract BACKGROUND Mycobacterium leprae, the causative agent of Hansen’s disease, causes neural damage through the specific interaction between the external phenolic glycolipid-1 (PGL-1) and laminin subunit alpha-2 (LAMA2) from Schwann cells. OBJECTIVE To design a LAMA2-based peptide that targets PGL-1 from M. leprae. METHODS We retrieved the protein sequence of human LAMA2 and designed a specific peptide using the Antimicrobial Peptide Database and physicochemical parameters for antimycobacterial peptide-lipid interactions. We used the AlphaFold2 server to predict its three-dimensional structure, AUTODOCK-VINA for docking, and GROMACS programs for molecular dynamics simulations. FINDINGS We analysed 52 candidate peptides from LAMA2, and subsequent screening resulted in a single 60-mer peptide. The mapped peptide comprises four β-sheets and a random coiled region. This peptide exhibits a 45% hydrophobic ratio, in which one-third covers the same surface. Molecular dynamics simulations show that our predicted peptide is stable in aqueous solution and remains stable upon interaction with PGL-1 binding. In addition, we found that PGL-1 has a preference for one of the two faces of the predicted peptide, which could act as the preferential binding site of PGL-1. MAIN CONCLUSIONS Our LAMA2-based peptide targeting PGL-1 might have the potential to specifically block this key molecule, suggesting that the preferential region of the peptide is involved in the initial contact during the attachment of leprosy bacilli to Schwann cells
Disciplines: Medicina
Keyword: Farmacología,
Bacterias,
Lepra,
Péptidos antimicrobianos,
Diseño de fármacos,
Mycobacterium leprae
Keyword: Pharmacology,
Bacteria,
Leprosy,
Mycobacterium leprae,
Antimicrobial peptides,
Drug design
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