{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:41:25Z","timestamp":1760146885798,"version":"build-2065373602"},"reference-count":48,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T00:00:00Z","timestamp":1735516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007956","name":"Natural Science Foundation of Nanjing University of Chinese Medicine","doi-asserted-by":"publisher","award":["XZR2023064"],"award-info":[{"award-number":["XZR2023064"]}],"id":[{"id":"10.13039\/501100007956","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The amphibian skin secretions are excellent sources of bioactive peptides, some of which and their derivatives exhibit multiple properties, including antibacterial and antagonism against bradykinin. A novel peptide Senegalin-2 was isolated from the skin secretions of Kassina senegalensis frog. Senegalin-2 relaxed rat bladder smooth muscle (EC50 17.94 nM) and ileum smooth muscle (EC50 135 nM), inhibited S. aureus and MRSA at 2 \u03bcM, and exhibited low hemolytic activity with no cytotoxicity. To design effective bradykinin antagonists, Senegalin-2 was conjugated with bradykinin to synthesize Senegalin-2BK. This modification retained potent activity against Gram-positive bacteria. Compared to Senegalin-2, Senegalin-2BK significantly reduced hemolysis and exhibited a more than threefold increase in the selectivity index. Furthermore, Senegalin-2BK contracted the bladder (EC50 2.83 \u03bcM) and ileum (EC50 56.64 nM)\u2019s smooth muscle. The pretreatment with 10\u22127 M Senegalin-2BK reduced the 10\u22126 M bradykinin contraction on the bladder by over 70%. In conclusion, Senegalin-2 has dual functionalities as an antibacterial agent and muscle relaxant, positioning it as a potential therapeutic candidate for managing overactive bladder. As a synthetically derived bradykinin antagonist and myotropic peptide with antibacterial properties, Senegalin-2BK shows promise in effective therapies for relieving pain, inflammation, and addressing muscular disorders such as urinary retention, constipation, and infections.<\/jats:p>","DOI":"10.3390\/biom15010030","type":"journal-article","created":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T12:37:19Z","timestamp":1735648639000},"page":"30","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Senegalin-2: A Novel Hexadecapeptide from Kassina senegalensis with Antibacterial and Muscle Relaxant Activities, and Its Derivative Senegalin-2BK as a Bradykinin Antagonist"],"prefix":"10.3390","volume":"15","author":[{"given":"Yueyang","family":"Lu","sequence":"first","affiliation":[{"name":"Jiangsu Clinical Innovation Center for Anorectal Diseases of T.C.M., Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing 210022, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanguo","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Queen\u2019s University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chengbang","family":"Ma","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Queen\u2019s University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8811-8489","authenticated-orcid":false,"given":"Lei","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Queen\u2019s University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2576-0252","authenticated-orcid":false,"given":"Mei","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Queen\u2019s University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8011-9260","authenticated-orcid":false,"given":"Tianbao","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Queen\u2019s University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaonan","family":"Ma","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Queen\u2019s University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xu","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Medicine and Life Sciences, Nanjing University of Chinese Medicine, Nanjing 210023, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhimin","family":"Fan","sequence":"additional","affiliation":[{"name":"Jiangsu Clinical Innovation Center for Anorectal Diseases of T.C.M., Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing 210022, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Cooper, S.L., Boyle, E., Jefferson, S.R., Heslop, C.R.A., Mohan, P., Mohanraj, G.G.J., Sidow, H.A., Tan, R.C.P., Hill, S.J., and Woolard, J. (2021). Role of the Renin-Angiotensin-Aldosterone and Kinin-Kallikrein Systems in the Cardiovascular Complications of COVID-19 and Long COVID. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22158255"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Lau, J., Rousseau, J., Kwon, D., B\u00e9nard, F., and Lin, K.S. (2020). A Systematic Review of Molecular Imaging Agents Targeting Bradykinin B1 and B2 Receptors. Pharmaceuticals, 13.","DOI":"10.3390\/ph13080199"},{"key":"ref_3","first-page":"1","article-title":"Basic and clinical aspects of bradykinin receptor antagonists","volume":"69","author":"Sharma","year":"2014","journal-title":"Prog. Drug Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"106305","DOI":"10.1016\/j.intimp.2020.106305","article-title":"Bradykinin receptors: Agonists, antagonists, expression, signaling, and adaptation to sustained stimulation","volume":"82","author":"Marceau","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Indriani, S., Karnjanapratum, S., Nirmal, N.P., and Nalinanon, S. (2023). Amphibian Skin and Skin Secretion: An Exotic Source of Bioactive Peptides and Its Application. Foods, 12.","DOI":"10.3390\/foods12061282"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/0010-406X(65)90007-1","article-title":"Occurrence of bradykinin in the skin of Rana temperaria","volume":"14","author":"Anastasi","year":"1965","journal-title":"Comp. Biochem. Physiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"951","DOI":"10.3390\/toxins7030951","article-title":"A review on bradykinin-related peptides isolated from amphibian skin secretion","volume":"7","author":"Xi","year":"2015","journal-title":"Toxins"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1002\/psc.2631","article-title":"Ornithokinin (avian bradykinin) from the skin of the Chinese bamboo odorous frog, Odorrana versabilis","volume":"20","author":"Lyu","year":"2014","journal-title":"J. Pept. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2886","DOI":"10.3390\/toxins6102886","article-title":"A novel bradykinin-related dodecapeptide (RVALPPGFTPLR) from the skin secretion of the Fujian large-headed frog (Limnonectes fujianensis) exhibiting unusual structural and functional features","volume":"6","author":"Shi","year":"2014","journal-title":"Toxins"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Wu, Y., Shi, D., Chen, X., Wang, L., Ying, Y., Ma, C., Xi, X., Zhou, M., Chen, T., and Shaw, C. (2019). A Novel Bradykinin-Related Peptide, RVA-Thr(6)-BK, from the Skin Secretion of the Hejiang Frog; Ordorrana hejiangensis: Effects of Mammalian Isolated Smooth Muscle. Toxins, 11.","DOI":"10.3390\/toxins11070376"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Zhou, X., Xu, J., Zhong, R., Ma, C., Zhou, M., Cao, Z., Xi, X., Shaw, C., Chen, T., and Wang, L. (2020). Pharmacological Effects of a Novel Bradykinin-Related Peptide (RR-18) from the Skin Secretion of the Hejiang Frog (Ordorrana hejiangensis) on Smooth Muscle. Biomedicines, 8.","DOI":"10.3390\/biomedicines8070225"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1007\/s00726-013-1470-8","article-title":"Senegalin: A novel antimicrobial\/myotropic hexadecapeptide from the skin secretion of the African running frog, Kassina senegalensis","volume":"44","author":"Wang","year":"2013","journal-title":"Amino Acids"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Du, Q., Wang, H., Ma, C., Wu, Y., Xi, X., Zhou, M., Chen, T., Shaw, C., and Wang, L. (2017). Identification of a Novel Vasodilatory Octapeptide from the Skin Secretion of the African Hyperoliid Frog, Kassina senegalensis. Molecules, 22.","DOI":"10.3390\/molecules22071215"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.molimm.2010.09.018","article-title":"Kassorins: Novel innate immune system peptides from skin secretions of the African hyperoliid frogs, Kassina maculata and Kassina senegalensis","volume":"48","author":"Chen","year":"2011","journal-title":"Mol. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2101","DOI":"10.1093\/bioinformatics\/btn392","article-title":"HELIQUEST: A web server to screen sequences with specific alpha-helical properties","volume":"24","author":"Gautier","year":"2008","journal-title":"Bioinformatics"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1093\/nar\/gky497","article-title":"BeStSel: A web server for accurate protein secondary structure prediction and fold recognition from the circular dichroism spectra","volume":"46","author":"Micsonai","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2960","DOI":"10.1016\/j.csbj.2023.05.006","article-title":"Discovery and analysis of a novel antimicrobial peptide B1AW from the skin secretion of Amolops wuyiensis and improving the membrane-binding affinity through the construction of the lysine-introduced analogue","volume":"21","author":"Qin","year":"2023","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Lin, Y., Jiang, Y., Zhao, Z., Lu, Y., Xi, X., Ma, C., Chen, X., Zhou, M., Chen, T., and Shaw, C. (2022). Discovery of a Novel Antimicrobial Peptide, Temporin-PKE, from the Skin Secretion of Pelophylax kl. esculentus, and Evaluation of Its Structure-Activity Relationships. Biomolecules, 12.","DOI":"10.3390\/biom12060759"},{"key":"ref_19","unstructured":"Al-Majed, A.A. (2021). Chapter Six\u2014Validation of in-vitro bioassay methods: Application in herbal drug research. Profiles of Drug Substances, Excipients and Related Methodology, Academic Press."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1038\/s41573-019-0058-8","article-title":"Antimicrobial host defence peptides: Functions and clinical potential","volume":"19","author":"Mookherjee","year":"2020","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1021\/cr4006704","article-title":"The chemistry and biological activities of peptides from amphibian skin secretions","volume":"115","author":"Xu","year":"2015","journal-title":"Chem. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1038\/s41467-017-01710-1","article-title":"Antimicrobial peptides in frog poisons constitute a molecular toxin delivery system against predators","volume":"8","author":"Raaymakers","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Xiang, J., Wang, H., Ma, C., Zhou, M., Wu, Y., Wang, L., Guo, S., Chen, T., and Shaw, C. (2016). Ex Vivo Smooth Muscle Pharmacological Effects of a Novel Bradykinin-Related Peptide, and Its Analogue, from Chinese Large Odorous Frog, Odorrana livida Skin Secretions. Toxins, 8.","DOI":"10.3390\/toxins8100283"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"26501","DOI":"10.1021\/acsami.6b08297","article-title":"Surface Physical Activity and Hydrophobicity of Designed Helical Peptide Amphiphiles Control Their Bioactivity and Cell Selectivity","volume":"8","author":"Chen","year":"2016","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1016\/j.bbamem.2018.03.021","article-title":"Hydrophobic interactions modulate antimicrobial peptoid selectivity towards anionic lipid membranes","volume":"1860","author":"Andreev","year":"2018","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.ijbiomac.2022.06.043","article-title":"Plant antimicrobial peptides: An overview about classification, toxicity and clinical applications","volume":"214","author":"Lima","year":"2022","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.tifs.2021.01.005","article-title":"The structure-mechanism relationship and mode of actions of antimicrobial peptides: A review","volume":"109","author":"Li","year":"2021","journal-title":"Trends Food Sci. Technol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"115377","DOI":"10.1016\/j.ejmech.2023.115377","article-title":"Antimicrobial peptides: Structure, mechanism, and modification","volume":"255","author":"Chen","year":"2023","journal-title":"Eur. J. Med. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2196","DOI":"10.1021\/acs.accounts.1c00047","article-title":"Advances in Molecular Understanding of \u03b1-Helical Membrane-Active Peptides","volume":"54","author":"Kabelka","year":"2021","journal-title":"Acc. Chem. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"112962","DOI":"10.1016\/j.lwt.2021.112962","article-title":"Discovery of novel antimicrobial peptides, Brevilaterin V, from Brevibacillus laterosporus S62-9 after regulated by exogenously-added L-valine","volume":"155","author":"Chen","year":"2022","journal-title":"LWT"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Decker, A.P., Mechesso, A.F., and Wang, G. (2022). Expanding the Landscape of Amino Acid-Rich Antimicrobial Peptides: Definition, Deployment in Nature, Implications for Peptide Design and Therapeutic Potential. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232112874"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"103282","DOI":"10.1016\/j.cis.2024.103282","article-title":"Advancements in peptide-based antimicrobials: A possible option for emerging drug-resistant infections","volume":"333","author":"Yadav","year":"2024","journal-title":"Adv. Colloid Interface Sci."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Agrillo, B., Porritiello, A., Gratino, L., Balestrieri, M., Proroga, Y.T., Mancusi, A., Cozzi, L., Vicenza, T., Dardano, P., and Miranda, B. (2023). Antimicrobial activity, membrane interaction and structural features of short arginine-rich antimicrobial peptides. Front. Microbiol., 14.","DOI":"10.3389\/fmicb.2023.1244325"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1097\/JU.0000000000002939","article-title":"Phenotyping of Urinary Urgency Patients Without Urgency Incontinence, and Their Comparison to Urgency Incontinence Patients: Findings from the LURN Study","volume":"209","author":"Lai","year":"2023","journal-title":"J. Urol."},{"key":"ref_35","first-page":"003781","article-title":"Oral anticholinergic drugs versus placebo or no treatment for managing overactive bladder syndrome in adults","volume":"5","author":"Stoniute","year":"2023","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.eururo.2023.05.014","article-title":"What Are the Short-term Benefits and Potential Harms of Therapeutic Modalities for the Management of Overactive Bladder Syndrome in Women? A Review of Evidence Under the Auspices of the European Association of Urology, Female Non-neurogenic Lower Urinary Tract Symptoms Guidelines Panel","volume":"84","author":"Farag","year":"2023","journal-title":"Eur. Urol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1152\/ajprenal.00048.2020","article-title":"Urinary bladder smooth muscle ion channels: Expression, function, and regulation in health and disease","volume":"319","author":"Malysz","year":"2020","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2083","DOI":"10.1007\/s00210-023-02786-x","article-title":"Effects of natural products on functional constipation: Analysis of active ingredient and mechanism","volume":"397","author":"Zhou","year":"2024","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"De La Franier, B., Asker, D., Hatton, B., and Thompson, M. (2022). Long-Term Reduction of Bacterial Adhesion on Polyurethane by an Ultra-Thin Surface Modifier. Biomedicines, 10.","DOI":"10.3390\/biomedicines10050979"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/nrurol.2011.194","article-title":"Role of potassium ion channels in detrusor smooth muscle function and dysfunction","volume":"9","author":"Petkov","year":"2012","journal-title":"Nat. Rev. Urol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1212\/NXI.0000000000000976","article-title":"Neuroprotective Properties of 4-Aminopyridine","volume":"8","author":"Dietrich","year":"2021","journal-title":"Neurol. Neuroimmunol. Neuroinflamm."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1002\/pro.2206","article-title":"Linkers in the structural biology of protein-protein interactions","volume":"22","author":"Kumar","year":"2013","journal-title":"Protein Sci."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Wang, Z., Teng, D., Mao, R., Hao, Y., Yang, N., Wang, X., and Wang, J. (2023). A cleavable chimeric peptide with targeting and killing domains enhances LPS neutralization and antibacterial properties against multi-drug resistant E. coli. Commun. Biol., 6.","DOI":"10.1038\/s42003-023-05528-0"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1016\/j.addr.2012.09.039","article-title":"Fusion protein linkers: Property, design and functionality","volume":"65","author":"Chen","year":"2013","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1038\/s41401-022-00982-8","article-title":"Function and structure of bradykinin receptor 2 for drug discovery","volume":"44","author":"Shen","year":"2023","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Ji, R.R., Cheng, J., and Ji, J. (2023). Inflammatory Mediators, Nociceptors, and Their Interactions in Pain. Neuroimmune Interactions in Pain, Springer.","DOI":"10.1007\/978-3-031-29231-6"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Smolinska, S., Antol\u00edn-Am\u00e9rigo, D., and Popescu, F.D. (2023). Bradykinin Metabolism and Drug-Induced Angioedema. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241411649"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.biotechadv.2014.11.005","article-title":"Synthetic fusion protein design and applications","volume":"33","author":"Yu","year":"2015","journal-title":"Biotechnol. Adv."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/1\/30\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:56:20Z","timestamp":1760115380000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/1\/30"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,30]]},"references-count":48,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["biom15010030"],"URL":"https:\/\/doi.org\/10.3390\/biom15010030","relation":{},"ISSN":["2218-273X"],"issn-type":[{"type":"electronic","value":"2218-273X"}],"subject":[],"published":{"date-parts":[[2024,12,30]]}}}