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The Neuroscientist : a Review Journal... Dec 2021Humans are an unusually prosocial species, who engage in social behaviors that include altruism-whereby an individual engages in costly or risky acts to improve the... (Review)
Review
Humans are an unusually prosocial species, who engage in social behaviors that include altruism-whereby an individual engages in costly or risky acts to improve the welfare of another person-care, and cooperation. Current perspectives on the neurobiology of human prosociality suggest that it is deeply rooted in the neuroendocrine architecture of the social brain and emphasize the modulatory role of the neuropeptide hormone oxytocin. In this review, we provide a conceptual overview of the neurobiology of prosocial behavior with a focus on oxytocin's modulatory role in human prosociality. Specifically, we aim to encourage a better understanding of the peptide's susceptibility to diverse factors that produce heterogeneity in outcomes and the resulting methodological implications for measuring the behavioral effects of oxytocin in humans. After providing an overview of the state-of-the-art research on oxytocin's exogenous use, we elaborate on the peptide's modulatory role in the context of care-based altruism, cooperation, and conflict and discuss its potential for therapeutic interventions in psychiatric disorders characterized by social dysfunction.
Topics: Altruism; Humans; Mental Disorders; Oxytocin; Social Behavior
PubMed: 32981445
DOI: 10.1177/1073858420960111 -
Methods in Molecular Biology (Clifton,... 2020The protection of amino acid reactive functionalities including the α-amino group, the side chain (amines, carboxylic acids, alcohols, and thiols), or the carboxylic...
The protection of amino acid reactive functionalities including the α-amino group, the side chain (amines, carboxylic acids, alcohols, and thiols), or the carboxylic acid terminus is an essential strategy in peptide chemistry. This is mandatory to prevent polymerization of the amino acids and to minimize undesirable side reactions during the synthetic process. Proper protecting group manipulation strategies can maximize the yield of the desired product or allow the construction of complex peptide-based structures. Thus, the compatibility and orthogonality of each protecting group are key to achieve the proper control of molecular structure. Herein, we describe some common protecting groups and their general unmasking methods, in order to mask and expose amine, carboxylic acid, alcohol, and thiol functionalities to achieve the synthesis of peptides and related molecules.
Topics: Amines; Amino Acids; Carboxylic Acids; Chemistry Techniques, Synthetic; Molecular Structure; Peptides; Solid-Phase Synthesis Techniques
PubMed: 31879921
DOI: 10.1007/978-1-0716-0227-0_7 -
Journal of Peptide Science : An... Aug 2021Sulfonopeptides as the sulfur analogues of natural peptides have been widely used as enzyme inhibitors due to their tetrahedral sulfonamide moiety, which can mimic the... (Review)
Review
Sulfonopeptides as the sulfur analogues of natural peptides have been widely used as enzyme inhibitors due to their tetrahedral sulfonamide moiety, which can mimic the transition-state analogues of hydrolysis of the ester and amide bonds. Synthetic methods of sulfonopeptides are reviewed. The synthetic methods of sulfonopeptides include the condensation of N-protected amino acid/peptide acids and 2-aminoalkanesulfonic acids, coupling of N-protected 2-aminoalkanesulfonyl chlorides and amino acid esters/peptide esters, sulfinylation of amino acid esters/peptide esters with N-protected 2-aminoalkanesulfinyl chlorides and subsequent oxidation, the alkylation of taurine-containing peptides, and the displacement of N-aminoacyl/peptidyl 2-aminoalkyl halides/methanesulfonates with sulfites. Hybrid sulfonophosphinopeptides are prepared through the Mannich-type reaction of N-protected 2-aminoalkanesulfonamides/peptidylsulfonamides, aldehydes, and aryldichlorophosphines/phosphorus trichloride followed by the aminolysis with amino acid/peptide esters or hydrolysis. The developed synthetic methods provide diverse synthetic routes for biologically important sulfonopeptides as the candidates of medicinal agents.
Topics: Molecular Structure; Peptides; Sulfhydryl Compounds
PubMed: 33913204
DOI: 10.1002/psc.3331 -
Molecules (Basel, Switzerland) May 2020In recent years, the peptide drug discovery field has shown a high level of dynamism, with hundreds of academic groups working on this topic, the creation of new...
In recent years, the peptide drug discovery field has shown a high level of dynamism, with hundreds of academic groups working on this topic, the creation of new peptide-focused companies, and the consolidation of peptide business by so-called big pharma [...].
Topics: Drug Discovery; Drug Industry; Humans; Peptides
PubMed: 32414106
DOI: 10.3390/molecules25102293 -
Alternative Therapies in Health and... Jul 2021Knee pain, a common complaint in primary care, has many causes, the most common of which is osteoarthritis (OA). Other common causes are meniscus tears, tendinosis,...
INTRODUCTION
Knee pain, a common complaint in primary care, has many causes, the most common of which is osteoarthritis (OA). Other common causes are meniscus tears, tendinosis, ligament tears or sprains, rheumatoid arthritis, lupus and septic arthritis. Also, referred pain from hip joint pathology like slipped capital femoral epiphysis can result in knee pain.1 The use of peptides BPC157 and thymosin-beta-4 (TB4) has not been studied in the treatment of knee pain.
METHODS
A retrospective study was done at the Institute for Hormonal Balance in Orlando, Florida, USA to see whether intra-articular injection of the peptide BPC 157, alone or combined with TB4, helped relieve knee pain. A 1-year chart review from 2019 to 2020 was performed. Since this was a retrospective study, patient follow-up varied, with most patients having had an injection of peptide into their knee 6 months to 1 year prior to the study. Of the 17 patients in the study, 16 were contacted by phone to follow up on the status of their knee pain. Only 1 patient could not be reached for the survey. Patients were asked to rate their pain prior to injection, the length of time the peptides helped ease the pain and the degree to which the injection helped them. No specific tools were used to measure their improvement in function, quality of life, stiffness or activities of daily living. The survey's main goal was to determine whether BPC157 helped with multiple types of knee pain in a primary care setting.
RESULTS
Of the 16 patients, 12 had received only BPC 157 as an intra-articular injection. In this group, 11 of the 12 patients (91.6%) had significant improvement in knee pain, whereas 1 patient (8.3 %) had no improvement. The other 4 patients received a combination of 2 peptide injections of BPC 157 and TB4. Of the patients who received both peptides, 75% showed significant improvement, but 25% had no relief of their knee pain. Overall, 14 of 16 patients (87.5%) had relief of their knee pain when BPC 157 or a combination of BPC 157 and TB4 was used.
CONCLUSION
This small study suggests that intra-articular injection of BPC-157 helps with multiple types of knee pain.
CLINICAL IMPLICATIONS
BPC157 is a peptide with regenerative properties that can be used to relieve multiple types of knee pain.2,3 Future studies are needed to look at the different causes of knee pain with follow-up magnetic resonance imaging scans (MRIs) to document the peptide's benefits. BPC157 has the potential to repair tears, build cartilage and reduce the number of knee surgeries. Because of its reparative properties, treatment with BPC157 offers advantages over the use of steroids.
RESULTS
BPC157 is a peptide with regenerative properties that can be used to relieve multiple types of knee pain.2,3 Future studies are needed to look at the different causes of knee pain with follow-up MRIs to document the peptide's benefits. BPC157 has the potential to repair tears, build cartilage and reduce the number of knee surgeries. Because of its reparative properties, treatment with BPC157 offers advantages over the use of steroids.
Topics: Activities of Daily Living; Humans; Injections, Intra-Articular; Osteoarthritis, Knee; Pain; Peptide Fragments; Proteins; Quality of Life; Retrospective Studies; Treatment Outcome
PubMed: 34324435
DOI: No ID Found -
Chimia Jun 2021The new Energypolis campus brings together the skills of EPFL Valais-Wallis, HES-SO Valais-Wallis, and the Ark Foundation's services. Together these partners respond to... (Review)
Review
The new Energypolis campus brings together the skills of EPFL Valais-Wallis, HES-SO Valais-Wallis, and the Ark Foundation's services. Together these partners respond to today's major concerns in the domains of energy, health, and the environment cutting-edge technology. The spirit of this new campus is to foster innovation in these disciplines and emulate the creation of start-up companies. The HES-SO hosts the School of Engineering (HEI) at this campus, which includes the following degree programmes: Life Technologies, Systems Engineering and Energy and Environmental Engineering, as well as their corresponding applied research institutes. Peptide technologies belong to the many activities that are carrying out in the Institute of Life Technologies. The present review summarizes the peptide technologies that are currently under development, that is, the regioselective labeling of therapeutic antibodies for cancer imaging, the development of peptide antivirals and antimicrobials for the treatment of infectious diseases, targeting of drugs conjugated to peptidic scaffolds as well as engineering of biomaterials.
Topics: Anti-Infective Agents; Peptides; Technology
PubMed: 34233821
DOI: 10.2533/chimia.2021.539 -
Journal of the American Chemical Society Aug 2023Cyclic peptides as a therapeutic modality are attracting a lot of attention due to their potential for oral absorption and accessibility to intracellular tough targets....
Cyclic peptides as a therapeutic modality are attracting a lot of attention due to their potential for oral absorption and accessibility to intracellular tough targets. Here, starting with a drug-like hit discovered using an mRNA display library, we describe a chemical optimization that led to the orally available clinical compound known as LUNA18, an 11-mer cyclic peptide inhibitor for the intracellular tough target RAS. The key findings are as follows: (i) two peptide side chains were identified that each increase RAS affinity over 10-fold; (ii) physico-chemical properties (PCP) including log can be adjusted by side-chain modification to increase membrane permeability; (iii) restriction of cyclic peptide conformation works effectively to adjust PCP and improve bio-activity; (iv) cellular efficacy was observed in peptides with a permeability of around 0.4 × 10 cm/s or more in a Caco-2 permeability assay; and (v) while keeping the cyclic peptide's main-chain conformation, we found one example where the RAS protein structure was changed dramatically through induced-fit to our peptide side chain. This study demonstrates how the chemical optimization of bio-active peptides can be achieved without scaffold hopping, much like the processes for small molecule drug discovery that are guided by Lipinski's rule of five. Our approach provides a versatile new strategy for generating peptide drugs starting from drug-like hits.
Topics: Humans; Proto-Oncogene Proteins p21(ras); Caco-2 Cells; Peptides; Peptides, Cyclic; Molecular Conformation
PubMed: 37463267
DOI: 10.1021/jacs.3c03886 -
Acta Biomaterialia Oct 2021Currently approved replication-competent and inactivated vaccines are limited by excessive reactogenicity and poor safety profiles, while subunit vaccines are often... (Review)
Review
Currently approved replication-competent and inactivated vaccines are limited by excessive reactogenicity and poor safety profiles, while subunit vaccines are often insufficiently immunogenic without co-administering exogenous adjuvants. Self-assembling peptide-, peptidomimetic-, and protein-based biomaterials offer a means to overcome these challenges through their inherent modularity, multivalency, and biocompatibility. As these scaffolds are biologically derived and present antigenic arrays reminiscent of natural viruses, they are prone to immune recognition and are uniquely capable of functioning as self-adjuvanting vaccine delivery vehicles that improve humoral and cellular responses. Beyond this intrinsic immunological advantage, the wide range of available amino acids allows for facile de novo design or straightforward modifications to existing sequences. This has permitted the development of vaccines and immunotherapies tailored to specific disease models, as well as generalizable platforms that have been successfully applied to prevent or treat numerous infectious and non-infectious diseases. In this review, we briefly introduce the immune system, discuss the structural determinants of coiled coils, β-sheets, peptide amphiphiles, and protein subunit nanoparticles, and highlight the utility of these materials using notable examples of their innate and adaptive immunomodulatory capacity. STATEMENT OF SIGNIFICANCE: Subunit vaccines have recently gained considerable attention due to their favorable safety profiles relative to traditional whole-cell vaccines; however, their reduced efficacy requires co-administration of reactogenic adjuvants to boost immune responses. This has led to collaborative efforts between engineers and immunologists to develop nanomaterial-based vaccination platforms that can elicit protection without deleterious side effects. Self-assembling peptidic biomaterials are a particularly attractive approach to this problem, as their structure and function can be controlled through primary sequence design and their capacity for multivalent presentation of antigens grants them intrinsic self-adjuvanticity. This review introduces the various architectures adopted by self-assembling peptides and discusses their application as modulators of innate and adaptive immunity.
Topics: Adaptive Immunity; Adjuvants, Immunologic; Antigens; Peptides; Vaccines, Subunit
PubMed: 34010691
DOI: 10.1016/j.actbio.2021.05.003 -
ChemMedChem Sep 2023Supramolecular assemblies made by the self-assembly of peptides are finding an increasing number of applications in various fields. While the early exploration of... (Review)
Review
Supramolecular assemblies made by the self-assembly of peptides are finding an increasing number of applications in various fields. While the early exploration of peptide assemblies centered on tissue engineering or regenerative medicine, the recent development has shown that peptide assemblies can act as supramolecular medicine for cancer therapy. This review covers the progress of applying peptide assemblies for cancer therapy, with the emphasis on the works appeared over the last five years. We start with the introduction of a few seminal works on peptide assemblies, then discuss the combination of peptide assemblies with anticancer drugs. Next, we highlight the use of enzyme-controlled transformation or shapeshifting of peptide assemblies for inhibiting cancer cells and tumors. After that, we provide the outlook for this exciting field that promises new kind of therapeutics for cancer therapy.
Topics: Humans; Peptides; Tissue Engineering; Antineoplastic Agents; Neoplasms
PubMed: 37380607
DOI: 10.1002/cmdc.202300258 -
Chemical Society Reviews Mar 2021Coacervates are condensed liquid-like droplets formed by liquid-liquid phase separation of molecules through multiple weak associative interactions. In recent years it... (Review)
Review
Coacervates are condensed liquid-like droplets formed by liquid-liquid phase separation of molecules through multiple weak associative interactions. In recent years it has emerged that not only long polymers, but also short peptides are capable of forming simple and complex coacervates. The coacervate droplets they form act as compartments that sequester and concentrate a wide range of solutes, and their spontaneous formation make coacervates attractive protocell models. The main advantage of peptides as building blocks lies in the functional diversity of the amino acid residues, which allows for tailoring of the peptide's phase separation propensity, their selectivity in guest molecule uptake and the physicochemical and catalytic properties of the compartments. The aim of this tutorial review is to illustrate the recent developments in the field of peptide-based coacervates in a systematic way and to deduce the basic requirements for both simple and complex coacervation of peptides. We review a selection of peptide coacervates that illustrates the essentials of phase separation, the limitations, and the properties that make peptide coacervates biomimetic protocells. Finally, we provide some perspectives of this novel research field in the direction of active droplets, moving away from thermodynamic equilibrium.
Topics: Artificial Cells; Biomimetics; Catalysis; Nucleotides; Peptides; Polyethylene Glycols
PubMed: 33616129
DOI: 10.1039/d0cs00307g