Abstract
Drug/polymer interactions occur during in situ polymerization of poly(alkylcyanoacrylate) (PACA) formulations. We have used MALDI ionization coupled tandem time-of-flight (TOF) mass spectrometry as an accurate method to characterize covalent peptide/polymer interactions of PACA nanoparticles with the bioactives D-Lys6-GnRH, insulin, [Asn1-Val5]-angiotensin II, and fragments of insulin-like growth factor 1 (IGF-1 (1-3)) and human adrenocorticotropic hormone (h-ACTH, (18-39)) at the molecular level. Covalent interactions of peptide with alkylcyanoacrylate were identified for D-Lys6-GnRH, [Asn1-Val5]-angiotensin II and IGF-1 (1-3). D-Lys6-GnRH and [Asn1-Val5]-angiotensin II were modified at their histidine side chain within the peptide, whilst IGF-1 (1-3) was modified at the C-terminal glutamic acid residue. The more complex protein insulin was not modified despite the presence of 2 histidine residues. This might be explained by the engagement of histidine residues in the folding and sterical arrangement of insulin under polymerization conditions. As expected, h-ACTH (18-39) that does not contain histidine residues did not interfere in the polymerization process. Lowering the pH did not prevent the covalent association of PACA with D-Lys6-GnRH or IGF-1 (1-3). Conclusively, protein and peptide bioactives are potentially reactive towards alkylcyanoacrylate monomers via various mechanisms with limited interference of pH. Histidines and C-terminal glutamic acid residues have been identified as potential sites of interaction. The likelihood of their engagement in the polymerization process (initiators), however, seems dependent on their sterical availability. The reactivity of nucleophilic functional groups should always be considered and bioactives examined for their potential to covalently interfere with alkylcyanoacrylate monomers, especially when designing PACA delivery systems for protein and peptide biopharmaceuticals.
Keywords: MALDI TOF/TOF, covalent conjugation, PACA, insulin, IGF-1, GnRH, angiotensin, h-ACTH
Current Drug Delivery
Title: Characterization of Peptide Polymer Interactions in Poly(alkylcyanoacrylate) Nanoparticles: A Mass Spectrometric Approach
Volume: 7 Issue: 3
Author(s): Alexandra P. Kafka, Torsten Kleffmann, Thomas Rades and Arlene McDowell
Affiliation:
Keywords: MALDI TOF/TOF, covalent conjugation, PACA, insulin, IGF-1, GnRH, angiotensin, h-ACTH
Abstract: Drug/polymer interactions occur during in situ polymerization of poly(alkylcyanoacrylate) (PACA) formulations. We have used MALDI ionization coupled tandem time-of-flight (TOF) mass spectrometry as an accurate method to characterize covalent peptide/polymer interactions of PACA nanoparticles with the bioactives D-Lys6-GnRH, insulin, [Asn1-Val5]-angiotensin II, and fragments of insulin-like growth factor 1 (IGF-1 (1-3)) and human adrenocorticotropic hormone (h-ACTH, (18-39)) at the molecular level. Covalent interactions of peptide with alkylcyanoacrylate were identified for D-Lys6-GnRH, [Asn1-Val5]-angiotensin II and IGF-1 (1-3). D-Lys6-GnRH and [Asn1-Val5]-angiotensin II were modified at their histidine side chain within the peptide, whilst IGF-1 (1-3) was modified at the C-terminal glutamic acid residue. The more complex protein insulin was not modified despite the presence of 2 histidine residues. This might be explained by the engagement of histidine residues in the folding and sterical arrangement of insulin under polymerization conditions. As expected, h-ACTH (18-39) that does not contain histidine residues did not interfere in the polymerization process. Lowering the pH did not prevent the covalent association of PACA with D-Lys6-GnRH or IGF-1 (1-3). Conclusively, protein and peptide bioactives are potentially reactive towards alkylcyanoacrylate monomers via various mechanisms with limited interference of pH. Histidines and C-terminal glutamic acid residues have been identified as potential sites of interaction. The likelihood of their engagement in the polymerization process (initiators), however, seems dependent on their sterical availability. The reactivity of nucleophilic functional groups should always be considered and bioactives examined for their potential to covalently interfere with alkylcyanoacrylate monomers, especially when designing PACA delivery systems for protein and peptide biopharmaceuticals.
Export Options
About this article
Cite this article as:
P. Kafka Alexandra, Kleffmann Torsten, Rades Thomas and McDowell Arlene, Characterization of Peptide Polymer Interactions in Poly(alkylcyanoacrylate) Nanoparticles: A Mass Spectrometric Approach, Current Drug Delivery 2010; 7 (3) . https://dx.doi.org/10.2174/156720110791560937
DOI https://dx.doi.org/10.2174/156720110791560937 |
Print ISSN 1567-2018 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5704 |
Call for Papers in Thematic Issues
Advances of natural products, bio-actives and novel drug delivery system against emerging viral infections
Due to the increasing prevalence of viral infections and the ability of these human pathogens to develop resistance to current treatment strategies, there is a great need to find and develop new compounds to combat them. These molecules must have low toxicity, specific activity and high bioavailability. The most suitable ...read more
Electrospun Fibers as Drug Delivery Systems
In recent years, electrospun fibers have attracted considerable attention as potential platforms for drug delivery due to their distinctive properties and adaptability. These fibers feature a notable surface area-to-volume ratio and can be intentionally designed with high porosity, facilitating an increased capacity for drug loading and rendering them suitable for ...read more
Emerging Nanotherapeutics for Mitigation of Neurodegenerative Disorders
Conditions affecting the central nervous system (CNS) present a significant hurdle due to limited access of both treatments and diagnostic tools for the brain. The blood-brain barrier (BBB) acts as a barrier, restricting the passage of molecules from the bloodstream into the brain. The most formidable challenge facing scientists is ...read more
Nanotechnology Based Chemotherapy for the treatment of Head & Neck Cancer
The escalating recurrence rates observed in Head and Neck cancer, particularly within the chemo-therapeutically treated cohort (50-60%), can be attributed to the non-selective nature of current anticancer drug delivery modalities. In this context, nanotechnology-based drug delivery systems emerge as a promising avenue for achieving precise localization of therapeutic agents to ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
CD93: Recent Advances and Implications in Disease
Current Drug Targets Structure Based Virtual Screening for the Identification of Potential Inhibitors for Penicillin Binding Protein 2B of the Resistant 5204 Strain of <i>Streptococcus pneumoniae</i>
Current Bioinformatics CT and CT-guided Percutaneous Needle Biopsy in Diagnosis of Primary Pulmonary Cryptococcosis in Immunocompetent Patients
Current Medical Imaging Molecular and Cellular Pathways as a Target of Therapeutic Hypothermia: Pharmacological Aspect
Current Neuropharmacology Drug Delivery Systems for Brain Tumor Therapy
Current Pharmaceutical Design Tandem Multicomponent Reactions Toward the Design and Synthesis of Novel Antibacterial and Cytotoxic Motifs
Current Medicinal Chemistry Serratia Type Pore Forming Toxins
Current Protein & Peptide Science Ribosome Inactivating Proteins (RIPs) from Momordica charantia for Anti Viral Therapy
Current Molecular Medicine Neurocysticercosis: The Enigmatic Disease
Central Nervous System Agents in Medicinal Chemistry Group A Streptococcal Infections in Children
Current Pediatric Reviews Gene Therapy to Improve Pancreatic Islet Transplantation for Type 1 Diabetes Mellitus
Current Diabetes Reviews Therapeutic Targets for the Prevention of Type 1 Diabetes Mellitus
Current Drug Targets - Immune, Endocrine & Metabolic Disorders Chemotherapy and Targeted Agents for Elderly Women with Advanced Breast Cancer
Recent Patents on Anti-Cancer Drug Discovery Separating Fact from Fiction: The Data Behind Allergies and Side Effects Caused by Penicillins, Cephalosporins, and Carbapenem Antibiotics
Current Pharmaceutical Design Clinical Interpretation of Drug Susceptibility Tests in Tuberculosis
Current Respiratory Medicine Reviews The Role of Adenosine in Rheumatoid Arthritis
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Natural Compounds Therapeutic Features in Brain Disorders by Experimental, Bioinformatics and Cheminformatics Methods
Current Medicinal Chemistry Evaluation of Vancoplus Versus Ceftriaxone Against Cephalosporin Resistance MRSA Strain in Experimental Meningitis Model
Cardiovascular & Hematological Disorders-Drug Targets Neurotrophic Factors in Combination: A Possible new Therapeutic Strategy to Influence Pathophysiology of Spinal Cord Injury and Repair Mechanisms
Current Pharmaceutical Design A Critical and Comprehensive Insight on Heme Oxygenase and Related Products Including Carbon Monoxide, Bilirubin, Biliverdin and Ferritin in Type-1 and Type-2 Diabetes
Current Pharmaceutical Design