Design and syntheses of peptidyl-urea analogs for catalysis and sensing applications

Abstract

Peptides and proteins play vital roles in almost all biological and physiological processes. Since they function as hormones, enzyme inhibitors or substrates, growth promoters, or inhibitors and neurotransmitters, life without them would be impossible. However, rapid degradation by proteases, poor oral availability, difficult transportation through cell membranes, nonselective receptor binding, and challenging multistep preparation are the major limitations of peptides. Hence, peptidomimetics via modifications of amino acids and amide bonds have been emerging to overcome the challenges present. The application of peptide chemistry is of burgeoning interest to diverse areas such as catalysis, drug delivery, development of sensors, and nanotechnology. Moreover, low molecular weight synthetic peptides are considered to be effective catalysts for an increasingly wide array of organic transformations. Also, short peptides comprising of urea moieties are showing their prominence for the development of efficient catalytic systems. Additionally, -NH units present in urea have proven as effective binding units for the development of various types of sensors. Therefore, keeping in view the fundamentals of peptidomimetic manipulations, herein, it is attempted to design and synthesize peptidyl-urea analogs for catalysis and sensing applications. The following chapters provide an overview of the current thesis and the content of each chapter is briefly discussed as follows. Chapter 1: Introduction This chapter starts with a review of peptide chemistry, including the structural and confirmational characteristics of the peptide bond. The current issues are then reviewed in depth, along with the manner in which they can be addressed via peptidomimetic manipulations such as amino acid and peptide bond modifications. In addition, the applications of short peptides in the field of material sciences, nanotechnology, biocatalysis and in supramolecular chemistry for the recognition of essential biomolecules have been highlighted. Finally, the literature review concludes with a discussion of the future work prospects. Chapter 2: Cytochrome c-Urea Functionalized Dipeptide Conjugate: An Efficient HBD Framework to Synthesize 4H-Pyrans via One-Pot Multicomponent Reaction Initially, protein-peptide conjugate (SS1-Cyt. c) is synthesized for the development of an efficient and green protocol, to synthesize a series of 4H-pyran derivatives. The whole assembly is used as an efficient catalytic system by incorporating a derivatized dipeptide molecule in the hydrophobic cavities of the protein Cytochrome c (Cyt. c) that leads to the activation of hydrogen bond donating (HBD) units of urea derivative of a dipeptide (SS1). The HBD units tend to show noncovalent interactions with the reactant species responsible for triggering the organic transformation to take place. The Eco-scale of 79 and E-factor of 0.089 is obtain on the green chemistry scale, and therefore the procedure considers to be an ecofriendly approach to produce 4H-pyran derivatives.Chapter 3: Urea-Functionalized Dipeptide Induced Allosteric Modulation for Tyrosinase Promiscuity: An Efficient Catalytic Assembly for facile Synthesis of Spiro-oxindoles In this chapter, the design and synthesis of a urea functionalized dipeptide molecule (SS2) is carried out which acts as an allosteric modulator and prompted the enzymatic promiscuity behavior of the widely spread orthologous tyrosinase enzyme (Tyr). The allosterically modified Tyr-SS2 hybrid is used as an efficient catalytic assembly for the synthesis of various spiro-oxindoles derivatives. The high yield of the products, i.e., up to 96 %, and with a less reaction time of 45 minutes are achieved. Simple purification steps reduce the reported literature's limitations. The Eco scale (80) and E-factors (0.096) calculations are in good agreement over the green chemistry scale, proving the developed strategy's sustainability and effectiveness. Chapter 4: Backbone Extension via Peptidomimetics at N-terminal; Selfassembled Nanofibrous Cluster and Application to Selective Progesterone Detection in an Aqueous Medium Despite the adequacy of the endogenous steroid (progesterone) levels in biological functioning, elevated levels of progesterone hormone have several physiological effects that are amplified due to its direct and indirect uptake from the environment, food products, and medical therapy. Therefore, it is much needed to evaluate the progesterone levels in environmental samples as well as for biological fluids. In this work, author focused on the development of the nano sensing probe for the selective detection of progesterone among the library of steroid hormones belonging to the class of female sex hormones. Herein, backbone extension via peptidomimetics is carried out at N-terminal to produce peptidyl-urea analog (SS3), and simultaneously, its self-assembly properties are explored. Moreover, to check the potency of the realtime application of the developed nanoprobe, successfully determination of the spiked concentration of progesterone levels in pharmaceutical and biological fluid samples achieved with good percentage recovery. Chapter 5: Solvent Directed Morphologies of Peptidic-Benzimidazolium Dipodal Receptor; Ratiometric Detection and Catalytic Degradation of Ochratoxin A Ochratoxin A (OTA) is the most abundant and harmful toxin found in agriculture and processed food. The environment and human health are both harmed by this mycotoxin. As a result, in various scenarios, selective detection and biodegradation of ochratoxin A are essential. The current study reveals the morphogenesis of a peptidic-benzimidazole dipodal receptor (SS4) and its application as a catalytic and sensing unit for the detection and degradation of OTA in an aqueous medium. Initially, a facile and scalable method was executed to synthesize SS4, and solventdirected morphologies were examined under SEM analysis. Consequently, molecular recognition properties of the self-assembled architectures were explored using UVVisible absorption, fluorescence spectroscopy, and atomic force microscopy (AFM). The developed probe showed ratiometric response for OTA and served as a catalytic unit for the degradation of OTA at a short interval of 25 min. The biodegradation pathway for OTA was depicted using LC-MS analysis. Furthermore, the reliability of the developed method ensured by determining the spiked concentrations of the OTA in cereals and wine samples. The results obtained are in good agreement with the % recovery and RSD values. The present work provides a robust, selective, and sensitive method of detection and degradation of OTA. Chapter 6: Conclusion This chapter discusses the thesis's silent features as well as the overall conclusion.