Sergei L Tikhonov, Olga O Babich, Stanislav A Sukhikh, Natalia V Tikhonova, Irina M Chernukha
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Peptide identification was performed using the MALDI-TOF MS Ultraflex method. Mass spectra were analyzed using the Mascot program. To confirm the efficiency of the algorithm, the antithrombin effect of the peptide was studied, which was evaluated by the activated partial thromboplastin time (APTT) of human citrate blood plasma coagulation.</p><p><strong>Results: </strong>A decision tree algorithm was developed to predict antithrombin activity and bioavailability of oral peptides. The top-down inductions of decision tree algorithms were used to create the algorithm. The decision tree is pruned if there is a mismatch in the peptide under study. Algorithm criteria or descriptors include amino acid sequence, number of amino acids, molecular weight, clinical potency, body distribution and metabolism index, plasma clearance, and half-life. According to the algorithm, if the result of \"Antithrombin Peptide\" is positive, it is concluded that it is bioavailable and effective for clinical use. To validate and evaluate the efficiency of the algorithm, a peptide containing antithrombin amino acid sequences was synthesized. The algorithm found the peptide to be antithrombin and bioavailable. The results of the biological activity of the peptide were confirmed in an in vitro experiment.</p><p><strong>Conclusion: </strong>Employing a decision tree method to assess the antithrombin activity and bioavailability of peptides can facilitate the development of effective oral peptides, hence minimizing the development time and the quantity of in vitro and in vivo studies required to validate efficacy.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":""},"PeriodicalIF":1.9000,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Prediction of Antithrombin Activity and Bioavailability of a Synthetic Peptide Using a Decision Tree Algorithm.\",\"authors\":\"Sergei L Tikhonov, Olga O Babich, Stanislav A Sukhikh, Natalia V Tikhonova, Irina M Chernukha\",\"doi\":\"10.2174/0113892037356348250523031542\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Thrombosis is a major cause of mortality from cardiovascular disease (CVD). The use of known antithrombin drugs is limited by the presence of side effects and complications. Peptides may be promising antithrombin agents.</p><p><strong>Objective: </strong>A peptide having the amino acid sequence QLSNGLFLFVDYLWW, designated as QW-13, was designed, synthesized, and used as a research object to evaluate the efficiency of the algorithm.</p><p><strong>Methods: </strong>The solid-phase Fmoc (SPPS) method, followed by purification by high-performance liquid chromatography (HPLC) was used for synthesis. The molecular weight distribution of the peptide was estimated by mass spectrometry. Peptide identification was performed using the MALDI-TOF MS Ultraflex method. Mass spectra were analyzed using the Mascot program. To confirm the efficiency of the algorithm, the antithrombin effect of the peptide was studied, which was evaluated by the activated partial thromboplastin time (APTT) of human citrate blood plasma coagulation.</p><p><strong>Results: </strong>A decision tree algorithm was developed to predict antithrombin activity and bioavailability of oral peptides. The top-down inductions of decision tree algorithms were used to create the algorithm. The decision tree is pruned if there is a mismatch in the peptide under study. Algorithm criteria or descriptors include amino acid sequence, number of amino acids, molecular weight, clinical potency, body distribution and metabolism index, plasma clearance, and half-life. According to the algorithm, if the result of \\\"Antithrombin Peptide\\\" is positive, it is concluded that it is bioavailable and effective for clinical use. To validate and evaluate the efficiency of the algorithm, a peptide containing antithrombin amino acid sequences was synthesized. The algorithm found the peptide to be antithrombin and bioavailable. 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引用次数: 0
摘要
背景:血栓形成是心血管疾病(CVD)死亡的主要原因。已知抗凝血酶药物的使用受到副作用和并发症的限制。多肽可能是很有前途的抗凝血酶药物。目的:设计合成一段氨基酸序列为QLSNGLFLFVDYLWW的肽,编号为QW-13,并以此为研究对象,对算法的效率进行评价。方法:固相Fmoc (SPPS)法合成,高效液相色谱法纯化。质谱法测定了肽的分子量分布。采用MALDI-TOF MS Ultraflex法进行多肽鉴定。质谱分析采用Mascot程序。为了验证算法的有效性,研究了该肽的抗凝血酶作用,并通过人柠檬酸盐血浆凝固的活化部分凝血活素时间(APTT)来评价该肽的抗凝血酶作用。结果:建立了一种预测口服多肽抗凝血酶活性和生物利用度的决策树算法。采用决策树算法的自顶向下归纳法创建算法。如果所研究的肽中存在不匹配,则对决策树进行修剪。算法标准或描述符包括氨基酸序列、氨基酸数量、分子量、临床效力、机体分布和代谢指数、血浆清除率和半衰期。根据该算法,如果“抗凝血酶肽”检测结果为阳性,则认为该药物具有生物利用度,可用于临床。为了验证和评价该算法的有效性,合成了含有抗凝血酶氨基酸序列的肽段。该算法发现该肽具有抗凝血酶和生物可利用性。体外实验证实了该肽的生物活性。结论:采用决策树方法评估多肽的抗凝血酶活性和生物利用度,有助于开发有效的口服多肽,从而最大限度地减少药效验证所需的体外和体内研究的开发时间和数量。
Prediction of Antithrombin Activity and Bioavailability of a Synthetic Peptide Using a Decision Tree Algorithm.
Background: Thrombosis is a major cause of mortality from cardiovascular disease (CVD). The use of known antithrombin drugs is limited by the presence of side effects and complications. Peptides may be promising antithrombin agents.
Objective: A peptide having the amino acid sequence QLSNGLFLFVDYLWW, designated as QW-13, was designed, synthesized, and used as a research object to evaluate the efficiency of the algorithm.
Methods: The solid-phase Fmoc (SPPS) method, followed by purification by high-performance liquid chromatography (HPLC) was used for synthesis. The molecular weight distribution of the peptide was estimated by mass spectrometry. Peptide identification was performed using the MALDI-TOF MS Ultraflex method. Mass spectra were analyzed using the Mascot program. To confirm the efficiency of the algorithm, the antithrombin effect of the peptide was studied, which was evaluated by the activated partial thromboplastin time (APTT) of human citrate blood plasma coagulation.
Results: A decision tree algorithm was developed to predict antithrombin activity and bioavailability of oral peptides. The top-down inductions of decision tree algorithms were used to create the algorithm. The decision tree is pruned if there is a mismatch in the peptide under study. Algorithm criteria or descriptors include amino acid sequence, number of amino acids, molecular weight, clinical potency, body distribution and metabolism index, plasma clearance, and half-life. According to the algorithm, if the result of "Antithrombin Peptide" is positive, it is concluded that it is bioavailable and effective for clinical use. To validate and evaluate the efficiency of the algorithm, a peptide containing antithrombin amino acid sequences was synthesized. The algorithm found the peptide to be antithrombin and bioavailable. The results of the biological activity of the peptide were confirmed in an in vitro experiment.
Conclusion: Employing a decision tree method to assess the antithrombin activity and bioavailability of peptides can facilitate the development of effective oral peptides, hence minimizing the development time and the quantity of in vitro and in vivo studies required to validate efficacy.
期刊介绍:
Current Protein & Peptide Science publishes full-length/mini review articles on specific aspects involving proteins, peptides, and interactions between the enzymes, the binding interactions of hormones and their receptors; the properties of transcription factors and other molecules that regulate gene expression; the reactions leading to the immune response; the process of signal transduction; the structure and function of proteins involved in the cytoskeleton and molecular motors; the properties of membrane channels and transporters; and the generation and storage of metabolic energy. In addition, reviews of experimental studies of protein folding and design are given special emphasis. Manuscripts submitted to Current Protein and Peptide Science should cover a field by discussing research from the leading laboratories in a field and should pose questions for future studies. Original papers, research articles and letter articles/short communications are not considered for publication in Current Protein & Peptide Science.