Harvesting the Potential of Peptoids for Various Applications Using Combinatorial Chemistry and Mass Spectrometry
Poster Number
1
Introduction/Abstract
Peptoids are also known as peptidomimetic material as the resemblance of their general structure with peptides. However, the fundamental difference is the position of the side chain on the nitrogen atom of the backbone instead of alpha carbon. The potential of peptoids for various applications can be harvested by generating combinations through combinatorial chemistry. Mass spectrometry is used to identify the unknown sequences in these libraries. We have used a bottom-up approach to understand the fragmentations of peptoids which in the future will help to establish the de novo sequencing of peptoids.
Purpose
Our study was aimed to understand the mysterious fragmentation pathways observed in protonated peptoids. In peptoids with basic side chains, we observed the peaks representing the loss of water from Y-ions. Also, some peaks represent the ions formed by the loss of neutral from the C terminus. The mechanism behind the loss of water is established by observing the absence of some ions while the loss of neutral occurs through the mobile protons from the Y-ions.
Method
Mass Spectrometry analysis is done using a Thermo Finnigan TSQ Quantum Mass Spectrometer. In a computational study, sequential geometry optimization and energy calculation at PM6 level, HF/3-21* and B3LYP/6-31+G**, were conducted after an initial conformer search. The mechanism underlying the loss of water is also understood by the Intrinsic Reaction Coordinate (IRC) study. To develop a clear understanding of peptoids fragmentation, the deuterium analog of some peptoids were also synthesized.
Results
In Peptoids with basic side chains, the loss of water occurs through the formation of five-membered cyclic hydroxylamine intermediate instead of a six-membered ring. Through computational chemistry, it is further confirmed that the key intermediate with the five-membered ring is 6kcal/mol more stable than the six-membered ring key intermediate. The loss of neutral from C terminus occurs through the secondary fragmentation of Y-Ions. Using deuterium analogues, it has been found that the proton source of Y-ions close to N terminus is the N-terminal amino group.
Significance
The incorporation of several different types of functional groups as a part of side chains in peptoids using combinatorial chemistry could hold a tremendous amount of potential for various applications. Mass Spectrometry plays a leading role in deconvoluting the Sequence of Peptoids in these libraries. Once the sequence is decoded, the structure-activity relationship could be easily established.
Location
DeRosa University Center
Format
Poster Presentation
Poster Session
Morning
Harvesting the Potential of Peptoids for Various Applications Using Combinatorial Chemistry and Mass Spectrometry
DeRosa University Center
Peptoids are also known as peptidomimetic material as the resemblance of their general structure with peptides. However, the fundamental difference is the position of the side chain on the nitrogen atom of the backbone instead of alpha carbon. The potential of peptoids for various applications can be harvested by generating combinations through combinatorial chemistry. Mass spectrometry is used to identify the unknown sequences in these libraries. We have used a bottom-up approach to understand the fragmentations of peptoids which in the future will help to establish the de novo sequencing of peptoids.
