Rational Design of Programmable Monodisperse Semi-Synthetic Protein Nanomaterials Containing Engineered Disulfide Functionality

Abstract

The reversible nature of disulfide functionality has been exploited to design intelligent materials such as nanocapsules, micelles, vesicles, inorganic nanoparticles, peptide and nucleic acid nanodevices. However, to our knowledge, there are no reports on design of semi-synthetic protein assemblies containing an engineered disulfide bond. Towards that end, herein, we disclose a new chemical methodology for the construction redox-sensitive protein assemblies using monodisperse facially amphiphilic protein-dendron bioconjugates. The disulfide functionality is strategically placed between the dendron and protein domains. The custom designed bioconjugates self-assembled into nanoscopic objects of a defined size dictated by the nature of dendron domain. The stimuli-responsive behavior of the protein assemblies is demonstrated using a suitable redox trigger.

Rational Design of Self-assembling Artificial Proteins Utilizing a Micelle-Assisted Protein Labeling Technology (MAPLabTech): Testing the Scope

“…Among the chemical technologies used for the design of well-defined monodisperse globular self-assembling artificial proteins, micelle-assisted protein labeling technology (MAPLabTech) has made enormous progress in the last 5 years 22–26 . The MAPLabTech 1.0 was effectively used for the synthesis of SAPs from the proteins belonging to the serine protease family.…”

“…Therefore, it is important to develop a general methodology that can incorporate a wide range of chemical entities onto the self-assembling proteins without compromising salient features of natural proteins such as a single chemical entity and the presence of well-defined functional groups in the 3d-space. Toward that goal, our group invented a new method called ‘Micelle-Assisted Protein Labeling Technology (MAPLabTech) 22–26 . During the last several years, we have utilized MAPLabTech for the design of different families of well-defined monodisperse globular SAPs which include protein amphiphiles 22 , protein-dendron conjugates 23 , protein-peptides conjugates 24 , photo-responsive protein amphiphiles 22 , multi-responsive protein-dendron conjugates 25 , and redox-sensitive protein conjugates 26 .…”

“…Toward that goal, our group invented a new method called ‘Micelle-Assisted Protein Labeling Technology (MAPLabTech) 22–26 . During the last several years, we have utilized MAPLabTech for the design of different families of well-defined monodisperse globular SAPs which include protein amphiphiles 22 , protein-dendron conjugates 23 , protein-peptides conjugates 24 , photo-responsive protein amphiphiles 22 , multi-responsive protein-dendron conjugates 25 , and redox-sensitive protein conjugates 26 . Although extremely powerful, the above method was only applicable to proteins that belong to the serine protease family 22–26 .…”

“…During the last several years, we have utilized MAPLabTech for the design of different families of well-defined monodisperse globular SAPs which include protein amphiphiles 22 , protein-dendron conjugates 23 , protein-peptides conjugates 24 , photo-responsive protein amphiphiles 22 , multi-responsive protein-dendron conjugates 25 , and redox-sensitive protein conjugates 26 . Although extremely powerful, the above method was only applicable to proteins that belong to the serine protease family 22–26 . This is a serious limitation and therefore restricts the use of this method for a variety of applications such as vaccine design 6,7 and antibody-drug conjugates.…”