<h3>Title</h3>
<h3>Rational design of Xenopeptides; steering towards biological activity</h3>
<p><strong><span style="text-decoration: underline;">Abstract</span> :</strong></p>
<p>Protein folding events are crucial steps that govern protein structure and function and can differ from one another. Some of these events are limited by kinetics and thermodynamics and determine the major hurdles for protein folding<sup>1</sup>. The introduction of a minimal sequence that can replicate the structure of such a key intermediate back into the protein externally during the protein folding event can alter this process. Such constrained peptide sequences, called xeno-peptides can have various biological implications depending upon the protein of interest. In the case of proteins like ubiquitin protein folding becomes faster in the presence of xeno-peptides, called a xeno-nuclei, as previously reported in our lab<sup>2</sup>. We have tried to make better xeno-peptide candidates for ubiquitin in this work and see if it can be observed in biological systems. The concept of xeno-peptides can have other relevant implications like turning these peptides into an antibiotic, inhibiting the function of relevant proteins in biological systems. We have designed xeno-peptides that can act as zippers that can inhibit functional beta-barrel outer membrane proteins in pathogens like gram-negative bacteria. This can open up a new regime of drug candidates having an entirely new modality of antibiotic activity which can help tackle the emerging antibiotic resistance. </p>
<p>1. Galzitskaya, O. V, Ivankov, D. N. &amp; Finkelstein, A. V. Folding nuclei in proteins. <em>FEBS Lett.</em> <strong>489</strong>, 113–118 (2001).</p>
<p>2. Das, A. <em>et al.</em> Rational Design of Protein-Specific Folding Modifiers. <em>J. Am. Chem. Soc.</em> <strong>143</strong>, 18766–18776 (2021).</p>
<p>3. A., F. M. &amp; T., W. C. Antibiotics for Emerging Pathogens. <em>Science (80-. ).</em> <strong>325</strong>, 1089–1093 (2009).</p>