Solid-Phase Organic Synthesis and Combinatorial Chemistry: A Laboratory Preparation of Oligopeptides

Truran, George A.; Aiken, Karelle; Fleming, Thomas; Webb, Peter J.; Markgraf, J. Hodge

doi:10.1021/ed079p85

Cited by 18 publications

(18 citation statements)

References 3 publications

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“…Students work in pairs to synthesize a hexapeptide of their own design following a modified version of a standard solid-phase peptide synthesis (SPPS) protocol. , This experiment is performed during three lab periods, over three consecutive weeks. Amino acids are coupled in the first 2 weeks.…”

Section: Experiments Summarymentioning

confidence: 99%

“…This activity differs from other peptide-based laboratory exercises previously published in this Journal in that the students have a large degree of ownership over the entire process. − Depending on the rubric used, this exercise is a narrow project-based or a level 1–2 type inquiry-based laboratory activity. ,, The coupling of a bioassay with the synthesis also makes this experiment unique. To begin, the students are provided with a problemantimicrobial resistanceand are introduced to the idea of antimicrobial peptides through a prelab video and a primary research paper. − The students are then guided through the process of developing a hypothesis and an experimental plan via a worksheet.…”

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confidence: 99%

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Searching for Synthetic Antimicrobial Peptides: An Experiment for Organic Chemistry Students

et al. 2016

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This laboratory experiment provides undergraduate students enrolled in organic chemistry the opportunity to design and synthesize their own peptide, which is then tested for antimicrobial activity. After reading a primary scientific paper on antimicrobial peptides, students design and synthesize their own hexapeptide that they hypothesize will have antimicrobial activity. The students characterize their products by analyzing liquid chromatography–mass spectrometry and antimicrobial bioassay data for their synthesized peptide. The students are able to complete the synthesis and prepare their samples for analysis in three 3–4 h lab periods; instructors perform LC–MS and a bioassay with the peptides and provide data to students for analysis. This exercise is flexible and can be altered to include students performing the bioassay, or to meet different time constraints or target student populations. This experiment allows students to increase their knowledge of solid phase peptide chemistry and gain experience with developing and testing hypotheses through experimental design.

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Section: Experiments Summarymentioning

confidence: 99%

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confidence: 99%

Searching for Synthetic Antimicrobial Peptides: An Experiment for Organic Chemistry Students

et al. 2016

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“…Numerous studies have highlighted the benefits of guided-inquiry and research project-based experiments in undergraduate chemistry laboratory courses. − The Distributed Drug Discovery (D3) program − is one of several initiatives that introduces organic chemistry students to drug discovery and combinatorial synthesis through course-based research projects. − By integrating targeted syntheses of bioactive molecules into teaching laboratories, the D3 program seeks to combine undergraduate chemistry education with broader research efforts in drug discovery. It also offers students hands-on experience with solid-phase synthesis, − complementing the solution-phase techniques typically taught in undergraduate laboratory courses . D3 chemistry protocols are designed to be robust, reproducible, and accessible to undergraduates in a variety of academic environments worldwide.…”

Section: Introductionmentioning

confidence: 99%

Globally Distributed Drug Discovery of New Antibiotics: Design and Combinatorial Synthesis of Amino Acid Derivatives in the Organic Chemistry Laboratory

et al. 2019

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An experiment for the synthesis of N-acyl derivatives of natural amino acids has been developed as part of the Distributed Drug Discovery (D3) program. Students use solid-phase synthesis techniques to complete a three-step, combinatorial synthesis of six products, which are analyzed using LC−MS and NMR spectroscopy. This protocol is suitable for introductory organic laboratory students and has been successfully implemented at multiple academic sites internationally. Accompanying prelab activities introduce students to SciFinder and to medicinal chemistry design principles. Pairing of these activities with the laboratory work provides students an authentic and cohesive research project experience.

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“…Interestingly, in some cases, SPPS was shown to be advantageous for synthesizing small molecules that are traditionally made in solution 32,33 . SPPS is used both in small scale for research and teaching 34,35 as well as large scale in industry [36][37][38] .…”

Section: Introductionmentioning

confidence: 99%

Development of a Backbone Cyclic Peptide Library as Potential Antiparasitic Therapeutics Using Microwave Irradiation

Qvit

Kornfeld

2016

JoVE

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Protein-protein interactions (PPIs) are intimately involved in almost all biological processes and are linked to many human diseases. Therefore, there is a major effort to target PPIs in basic research and in the pharmaceutical industry. Protein-protein interfaces are usually large, flat, and often lack pockets, complicating the discovery of small molecules that target such sites. Alternative targeting approaches using antibodies have limitations due to poor oral bioavailability, low cell-permeability, and production inefficiency. Using peptides to target PPI interfaces has several advantages. Peptides have higher conformational flexibility, increased selectivity, and are generally inexpensive. However, peptides have their own limitations including poor stability and inefficiency crossing cell membranes. To overcome such limitations, peptide cyclization can be performed. Cyclization has been demonstrated to improve peptide selectivity, metabolic stability, and bioavailability. However, predicting the bioactive conformation of a cyclic peptide is not trivial. To overcome this challenge, one attractive approach it to screen a focused library to screen in which all backbone cyclic peptides have the same primary sequence, but differ in parameters that influence their conformation, such as ring size and position. We describe a detailed protocol for synthesizing a library of backbone cyclic peptides targeting specific parasite PPIs. Using a rational design approach, we developed peptides derived from the scaffold protein Leishmania receptor for activated C-kinase (LACK). We hypothesized that sequences in LACK that are conserved in parasites, but not in the mammalian host homolog, may represent interaction sites for proteins that are critical for the parasites' viability. The cyclic peptides were synthesized using microwave irradiation to reduce reaction times and increase efficiency. Developing a library of backbone cyclic peptides with different ring sizes facilitates a systematic screen for the most biological active conformation. This method provides a general, fast, and facile way to synthesize cyclic peptides.

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Solid-Phase Organic Synthesis and Combinatorial Chemistry: A Laboratory Preparation of Oligopeptides

Cited by 18 publications

References 3 publications

Searching for Synthetic Antimicrobial Peptides: An Experiment for Organic Chemistry Students

Searching for Synthetic Antimicrobial Peptides: An Experiment for Organic Chemistry Students

Globally Distributed Drug Discovery of New Antibiotics: Design and Combinatorial Synthesis of Amino Acid Derivatives in the Organic Chemistry Laboratory

Development of a Backbone Cyclic Peptide Library as Potential Antiparasitic Therapeutics Using Microwave Irradiation

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