Structural Modification of Proteins and Peptides

Abstract

Proteins and peptides are ubiquitous in every cell and thus are vital for various biological functions. In recent years, there is an extensive growth in the development of various biologicals and large molecules like proteins and peptides. Now, they are replacing the market of existing organic based pharmaceuticals. This review article intends to summarize various structural modifications that are carried out in order to alter basic properties of peptides and proteins so that their solubility, absorption, permeability and various other problems associated with their delivery can be resolved. Thus they can offer significant therapeutic potential.

Improvements in chemical carriers of proteins and peptides

“…Chemical modification could provide a more efficient uptake of cargoes across the epithelial barrier of the gastrointestinal tract (Buckley et al, 2016). In addition, modification of proteins and peptides structurally not only improved drug delivery, but also it could enhance patient compliance (Mahajan et al, 2014). For feasible delivery of proteins and peptides through oral route, their physicochemical properties (e.g., stability, hydrophobicity and molecular weight) as well as biological barriers (e.g., proteolysis in stomach and poor permeation into cells) should be considered.…”

“…Generally, structural modifications of proteins and peptides include prodrug, analogous formation, modification of C-or N-terminals (e.g., polymer conjugation, post-terminal modification, site specific modification), conjugation with fatty acids (e.g., irreversible lipidization, reversible lipidization), combination of both site-specific modification and lipidization, hydrophobic ion pairing, complexation with cyclodextrins, and current technologies (e.g., Nobex technology, Emisphere technology) (Mahajan et al, 2014). Briefly, the importance of structural modification includes: a) To change the solubility, stability, crystallinity and targetability of drug; b) To enhance the hydrolytic and enzymatic stability; c) To improve the permeability across intestinal epithelia; d) To increase the plasma half life of protein; e) To prolong the residence time in the body; f) To reduce or eliminate the protein immunogenicity (Mahajan et al, 2014). These issues could be solved by modification of the physicochemical property or the use of a delivery system.…”

“…In fact, proteins interact with different compounds in biological environment which influence their biological activity, absorption, and biodistribution (Mahajan et al, 2014). Moreover, enzymatic degradation influences the absorption and half life of peptides in the body especially in acid environment of gastrointestinal tract.…”

“…Furthermore, peptides were utilized to treat different types of diseases including cancers, infectious diseases or endocrine dysfunctions. Some commercially proteins and peptides include bradykinin, angiotensinII, atrial natriuretic peptide, deslorelin (Somagard), denileukindiftitox (Ontak), interleukin-2 (Tecaleukin), interferon a-2a (Referon A), secretin (secretin ferring), pentagastrin (peptavion), thymopentin timunox (timunox), exenatide, insulin, peginterferon a-2a, pegfilgrastim, and peginterferon a-2b (Gupta and Sharma, 2009;Mahajan et al, 2014). Some commercially proteins and peptides include bradykinin, angiotensinII, atrial natriuretic peptide, deslorelin (Somagard), denileukindiftitox (Ontak), interleukin-2 (Tecaleukin), interferon a-2a (Referon A), secretin (secretin ferring), pentagastrin (peptavion), thymopentin timunox (timunox), exenatide, insulin, peginterferon a-2a, pegfilgrastim, and peginterferon a-2b (Gupta and Sharma, 2009;Mahajan et al, 2014).…”

A Review on Recent Advances in Stabilizing Peptides/Proteins upon Fabrication in Hydrogels from Biodegradable Polymers

“…Regarding peptides two amino acids are condensed to form dipeptides, three join to forms tripeptides, four form tetrapeptide and those that contain 2-20 amino acids are polypeptides [33][34][35][36].Every cell contains proteins and peptides that play a unique role in various biological functions. Recently the development of biological compounds and giant molecules like proteins and peptides have increased to a greater extent and have taken the place of organic compound used as pharmaceuticals [37]. Novel sustained release formulations of peptides and proteins provide better opportunities for the cure and prevention of disease.…”