Comparative analysis of new peptide conjugates of antitubercular drug candidates—Model membrane and in vitro studies

Ábrahám, Zs Baranyai, G. Gyulai, E. Pári, K. Horváti, Sz. Bősze, E. Kiss

Research output: Article

4 Citations (Scopus)

Abstract

Novel peptide conjugates of two antitubercular drug candidates were synthesised and characterised using new tuftsin peptide derivative (OT14) as carrier moiety. As antitubercular drug candidates two pyridopyrimidine derivatives, TB803 (2-allylamino-4-oxopyrido[1,2-a]pyrimidine-3-carbaldehyde) and TB820 (4-oxo-2-(pyrrolidin-1-yl)-pyrido[1,2-a]pyrimidin-3-carbaldehyde) inhibiting vital enzyme of Mycobacterium tuberculosis were applied. Membrane affinity of the compounds TB803 and TB820 and their peptide conjugates was evaluated using experimental lipid mono- and bilayer models. Penetration ability was assessed tensiometrically from Langmuir monolayer study and applying quartz crystal microbalance for the supported lipid bilayer (SLB) system. Minimal inhibitory concentration (MIC) values remained in a similar micromolar range for both of the conjugates while their cellular uptake rate was improved significantly compared to the drug candidates. A correlation was found between membrane affinity properties and results of in vitro biological investigations. Analysis of physical/structural properties of SLB in contact with bioactive components and visualization of the structural change by atomic-force microscopy (AFM) provided information on the type and route of molecular interaction of drug construction with lipid layers. The possible role of electrostatic interactions between lipid layer and drug candidates was tested in Langmuir-balance experiments using negatively charged lipid mixture (DPPC + DPPG). Especially the peptide conjugates presented increased membrane affinity due to cationic character of the peptide sequence selected for the conjugate formation. That is supposed to be one reason for the enhanced cellular uptake observed in vitro on MonoMac6 cell line. The conjugation of antitubercular agents to a peptidic carrier is a promising approach to enhance membrane affinity, cellular uptake rate and in vitro selectivity.

Original languageEnglish
Pages (from-to)106-115
Number of pages10
JournalColloids and Surfaces B: Biointerfaces
Volume147
DOIs
Publication statusPublished - nov. 1 2016

Fingerprint

Antitubercular Agents
Peptides
peptides
lipids
drugs
Lipids
membranes
Membranes
Lipid Bilayers
affinity
Lipid bilayers
Monolayers
Tuftsin
Quartz Crystal Microbalance Techniques
Pharmaceutical Preparations
Derivatives
Molecular interactions
Atomic Force Microscopy
Quartz crystal microbalances
tuberculosis

ASJC Scopus subject areas

  • Biotechnology
  • Medicine(all)
  • Surfaces and Interfaces
  • Physical and Theoretical Chemistry
  • Colloid and Surface Chemistry

Cite this

Comparative analysis of new peptide conjugates of antitubercular drug candidates—Model membrane and in vitro studies. / Ábrahám; Baranyai, Zs; Gyulai, G.; Pári, E.; Horváti, K.; Bősze, Sz.; Kiss, E.

In: Colloids and Surfaces B: Biointerfaces, Vol. 147, 01.11.2016, p. 106-115.

Research output: Article

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