Over the lifespan of therapeutic proteins, from the point of biosynthesis to the complete clearance from tested subjects, they undergo various biological modifications. Therapeutic influences and molecular mechanisms of these modifications have been well appreciated for some while remained less understood for many. This paper has classified these modifications into multiple categories, according to their processing locations and enzymatic involvement during the trafficking events. It also focuses on the underlying mechanisms and structural-functional relationship between modifications and therapeutic properties. In addition, recent advances in protein engineering, cell line engineering, and process engineering, by exploring these complex cellular processes, are discussed and summarized, for improving functional characteristics and attributes of protein-based biopharmaceutical products.
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http://dx.doi.org/10.1155/2013/273086 | DOI Listing |
Drugs
January 2025
Division of Endocrinology, Department of Pediatrics, College of Medicine, University of Florida, 1699 SW 16th Ave, Building A, Gainesville, FL, 32608, USA.
Type 1 diabetes mellitus (T1DM) is characterized by the progressive, autoimmune-mediated destruction of β cells. As such, restoring immunoregulation early in the disease course is sought to retain endogenous insulin production. Nevertheless, in the more than 100 years since the discovery of insulin, treatment of T1DM has focused primarily on hormone replacement and glucose monitoring.
View Article and Find Full Text PDFBiochemistry
January 2025
Department of Biochemistry, Genetics and Microbiology, Faculty of Natural and Agricultural Sciences, University of Pretoria, Pretoria 0002, South Africa.
C-terminal amidation of antimicrobial peptides (AMPs) is a frequent minor modification used to improve antibacterial potency, commonly ascribed to increased positive charge, protection from proteases, and a stabilized secondary structure. Although the activity of AMPs is primarily associated with the ability to penetrate bacterial membranes, hitherto the effect of amidation on this interaction has not been understood in detail. Here, we show that amidation of the scorpion-derived membranolytic peptide AamAP1-Lys produces a potent analog with faster bactericidal activity, increased membrane permeabilization, and greater Gram-negative membrane penetration associated with greater conformational flexibility.
View Article and Find Full Text PDFNanoscale
January 2025
Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an 710054, China.
MXenes, with their good biocompatibility, excellent photovoltaic properties, excellent physicochemical properties, and desirable bioactivity, have broad application prospects in the field of tissue regeneration. MXenes have been used in a wide range of applications including biosensing, bioimaging, tumour/infection therapy, bone regeneration and wound repair. By applying bioactive materials to modify the surface of MXenes, a series of multifunctional MXene-based nanomaterials can be designed for different biomedical applications to achieve better therapeutic effects or more desirable biological functions.
View Article and Find Full Text PDFLife Med
August 2024
Department of Hepatobiliary Surgery, Xi-Jing Hospital, Fourth Military Medical University, Changle West Road, Xincheng District, Xi'an, Shaanxi 710032, China.
Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver condition, characterized by a spectrum that progresses from simple hepatic steatosis to nonalcoholic steatohepatitis, which may eventually lead to cirrhosis and hepatocellular carcinoma. The precise pathogenic mechanisms underlying NAFLD and its related metabolic disturbances remain elusive. Epigenetic modifications, which entail stable transcriptional changes without altering the DNA sequence, are increasingly recognized as pivotal.
View Article and Find Full Text PDFCureus
December 2024
Neurosurgery, Federal Fluminense University, Niterói, BRA.
The coexistence of type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) represents a significant global health challenge, contributing to substantial morbidity, mortality, and economic burden. T2DM is the leading cause of CKD, and CKD exacerbates diabetes-related complications, creating a bidirectional relationship driven by oxidative stress, inflammation, and endothelial dysfunction. Diabetic kidney disease (DKD), affecting some individuals with T2DM, accelerates progression to end-stage renal disease (ESRD) and increases cardiovascular mortality.
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