CAREER: Combinatorial Neoglycopeptide Arrays: Synthesis and Application Toward Creating Bioactive Peptides Resistant to Proteolysis

圣克拉拉大学化学系的Michael Carrasco教授得到了有机和大分子化学项目的支持，他的研究是确定肽和蛋白质如何通过糖或其他小有机分子的附着而抵抗蛋白质水解。通过研究最近开发的组合方法合成的新糖肽阵列，卡拉斯科教授希望发现赋予蛋白质水解抗性的一般结构基序。然后，这些基序将在实践和理论兴趣的肽和蛋白质模型上进行测试。研究的阶段将是：(1)合成新糖肽组合阵列，(2)确定各种蛋白酶对新糖肽阵列成员的蛋白水解，(3)分析结果以确定一般的保护性结构基序，以及(4)将这些基序引入生物活性肽和蛋白质中以增加其蛋白水解抗性而不干扰其功能。所产生的结果将为新型肽和蛋白质药物的设计提供新的策略。该提案的教学部分侧重于扩展科学研究文化和学者社区，包括代表性不足的学生，特别强调拉丁裔学生。将实施四个具体目标，以促进跨科学学科的学生和教师网络，以解决一般科学问题和来自多元文化背景的特定辅助问题。这四个目标是：(1)从代表性不足的群体中识别和招募研究学生；(2)创建一个教师和同伴指导网络；(3)建立一个具体的研究报告计划，并参加地区和国家会议；(4)发起一个由代表性不足的群体的杰出科学家举办的定期特别系列研讨会。该计划的主要重点是为学生提供科学和个人指导。因此，在有机和大分子化学项目的支持下，圣克拉拉大学化学系的Michael Carrasco教授试图确定糖基化是否可以作为开发更多蛋白水解抗性肽和蛋白质药物的有效工具，作为他研究工作的一部分，并将教学和指导代表性不足的学生作为他教育目标的一部分。

Professor Michael Carrasco, of the Department of Chemistry at Santa Clara University, is supported by the Organic and Macromolecular Chemistry Program for his studies to determine how peptides and proteins can be made resistant to proteolysis by the attachment of sugars or other small organic molecules. By studying arrays of neoglycopeptides synthesized by a recently developed combinatorial method, Professor Carrasco hopes to discover general structural motifs that confer proteolytic resistance. These motifs will then be tested on peptide and protein models of practical and theoretical interest. The stages of research will be: (1) synthesizing a combinatorial array of neoglycopeptides, (2) determining the proteolysis of the members of the neoglycopeptide array by a variety of proteases, (3) analyzing the results to determine general, protective structural motifs, and (4) introducing these motifs to bioactive peptides and proteins to increase their proteolytic resistance without disturbing their function. The results generated will provide new strategies for the design of novel peptide and protein pharmaceuticals.The teaching portion of this proposal focuses on extending the culture of research and community of scholars present in the sciences to include underrepresented students with a special emphasis on Latino students. Four concrete objectives will be implemented to foster a network of students and faculty across the scientific disciplines that will address both general scientific issues and ancillary issues specific to those from multicultural backgrounds. The four objectives are: (1) identifying and recruiting research students from underrepresented groups, (2) creating a faculty and peer mentoring network, (3) establishing a specific program of research presentations and attendance at regional and national meetings, and (4) initiating a regular, special seminar series given by prominent scientists from underrepresented groups. The main emphasis of the program is providing both scientific and personal mentoring for the students. Therefore, with the support of the Organic and Macromolecular Chemistry Program for this CAREER award, Professor Michael Carrasco, of the Department of Chemistry at the Santa Clara University seeks to determine if glycosylation can be an effective tool in developing more proteolytic-resistant peptide and protein pharmaceutical as part of his research effort and will use teaching and mentoring underrepresented students as part of his educational goals.