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教授得到了有机和高分子化学计划的支持，他的研究确定了如何通过附着糖或其他有机小分子来使多肽和蛋白质抵抗蛋白质分解。通过研究最近开发的一种组合方法合成的一系列新糖肽，卡拉斯科教授希望发现赋予蛋白分解抗性的一般结构基序。这些模体随后将在具有实际和理论意义的多肽和蛋白质模型上进行测试。研究的阶段将是：(1)合成新糖肽的组合阵列，(2)测定新糖肽阵列的成员被各种蛋白酶的蛋白质分解，(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多肽和蛋白质中，以在不干扰其功能的情况下增加它们的蛋白分解抗性。所产生的结果将为新的多肽和蛋白质药物的设计提供新的战略。这项建议的教学部分侧重于扩大研究文化和科学界的学者社区，以包括代表性不足的学生，并特别强调拉丁裔学生。将实施四个具体目标，以培养跨科学学科的学生和教职员工网络，既解决一般科学问题，也解决那些来自多文化背景的人特有的辅助问题。四个目标是：(1)从代表性不足的群体中确定和招募研究型学生，(2)创建教师和同行指导网络，(3)建立研究报告和出席区域和国家会议的具体方案，以及(4)发起由代表性不足群体中的杰出科学家举办的定期特别研讨会系列。该项目的主要重点是为学生提供科学指导和个人指导。因此，在有机和高分子化学计划的支持下，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他的研究工作的一部分，作为他的研究工作的一部分，并将教学和指导未被充分代表的学生作为他的教育目标的一部分，以确定糖基化是否可以作为开发更多抗蛋白水解肽和蛋白质药物的有效工具。

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.