Molecular Architectonics of Cyclic Dipeptide Amphiphiles and Their Application in Drug Delivery

• Assembly and co-assemblies of peptide amphiphiles through specific noncovalent forces expand the space of molecular architectonics-driven construction of diverse nanoarchitectures with potential biological applications. In this work, cyclic dipeptide amphiphiles (CDPAs) of cyclo(Gly-Asp) with varying lengths of alkyl chains (C8-C18) were synthesized, and their molecular organization was studied. The noncovalent interactions of the components, CDP and alkyl chain, drive the molecular self-assembly of CDPAs into well-defined and diverse nanoarchitectures such as nanotubes, nanospheres, nano/microsheets, and flowers. The co-assembly of CDPAs with biological molecules such as nucleosides was studied to ascertain their utility as potential drug delivery vehicles. Mechanical properties of these nanoarchitectures in nanoindentation study established them as robust in nature. A temperature-dependent NMR study confirmed the formation of stable co-assembly of CDPAs, primarily driven by the intermolecular hydrogen bonding interactions. Computational modeling of oligomers of CDPAs and their co-assembly with nucleosides/nucleotides reveal the molecular level interactions and driving force behind such assemblies. CDPAs exhibit good biocompatibility and cytocompatibility, as revealed by the cellular studies which substantiated their suitability for drug delivery applications. The co-assembly of CDPA with an anticancer drug 5-bromo-2′-deoxyuridine (BrdU) was studied as a drug delivery platform and cytotoxicity was successfully assessed in HeLa cells. Computational modeling of the oligomers of CDPAs and their co-assembly with the drug molecule was performed to understand the molecular level interactions and driving force behind the assemblies. Our findings reveal the design strategy to construct diverse structural architectures using CDP as the modular building unit and specific molecular interactions driven co-assembly for potential application as drug delivery carrier. 

Subject headings

NATURVETENSKAP  -- Kemi -- Annan kemi (hsv//swe)

NATURAL SCIENCES  -- Chemical Sciences -- Other Chemistry Topics (hsv//eng)

Keyword

cyclic dipeptide amphiphile

drug delivery

molecular architectonics

nanoarchitecture

nanoindentation

Amphiphiles

Biocompatibility

Biomolecules

Computation theory

Drug interactions

Hydrogen bonds

Ions

Lanthanum compounds

Modular construction

Molecules

Oligomers

Peptides

Targeted drug delivery

Biological applications

Drug delivery applications

Intermolecular hydrogen bonding

Molecular level interactions

Molecular organization

Molecular self assembly

Non-covalent interaction

Structural architecture

Controlled drug delivery

Publication and Content Type

ref (subject category)

art (subject category)