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In the realm of medicinal chemistry, heterocyclic compounds play a vital role due to their diverse pharmacological properties, especially, pyrroloindoles standing out as crucial motifs in drug development. Pyrroloindoles, which are formed by combining indole and pyrrole rings, exhibit unique characteristics and serve as integral components in numerous drugs and natural compounds. The synthesis of pyrroloindoles is challenging due to their complex ring structures and diverse substitution patterns. This comprehensive review compiles various synthetic strategies for obtaining pyrroloindole derivatives via metal‐catalyzed reactions; cyclopropanation/ ring opening/ iminium cyclization (CRI reaction); organocatalytic cascade addition‐cyclization; 1,3‐dipolar cycloaddition; Brønsted acid‐catalyzed [3+2] cyclodimerization; ring closure mechanisms; thermally‐induced ring‐opening and cyclization reactions; condensation reactions; and visible‐light photocatalytic asymmetric reactions providing a valuable resource for synthetic organic chemists and researchers interested in the synthesis of pyrroloindoles and their derivatives. These compounds play a pivotal role in drug discovery thus, making this review an indispensable reference. [ABSTRACT FROM AUTHOR]

Peptide-based drugs are gaining significant momentum in the modern drug discovery, which is witnessed by the approval of new drugs by the FDA in recent years. On the other hand, small molecules-based drugs are an integral part of drug development since the past several decades. Peptide-containing drugs are placed between small molecules and the biologics. Both the peptides as well as the small molecules (mainly heterocycles) pose several drawbacks as therapeutics despite their success in curing many diseases. This gap may be bridged by utilising the so called 'conjugation chemistry', in which both the partners are linked to one another through a stable chemical bond, and the resulting conjugates are found to possess attracting benefits, thus eliminating the stigma associated with the individual partners. Over the past decades, the field of molecular hybridisation has emerged to afford us new and efficient molecular architectures that have shown high promise in medicinal chemistry. Taking advantage of this and also considering our experience in this field, we present herein a review concerning the molecules obtained by the conjugation of peptides (amino acids) to small molecules (heterocycles as well as bioactive compounds). More than 125 examples of the conjugates citing nearly 100 references published during the period 2000 to 2022 having therapeutic applications in curing infectious diseases have been covered. [ABSTRACT FROM AUTHOR]

Pyrroloindoles are therapeutically important, and there are various methods for synthesizing their derivatives. The review by Suhas Ramesh and co‐workers highlights various synthetic methodologies, including metal‐catalyzed reactions, organocatalytic cascade addition‐cyclization, etc...By Sanjay S. Ramesh; Rohith Gattu and Suhas RameshReported by Author; Author; Author [Extracted from the article]

Peptides of relatively low charge and a high number of hydrophobic amino acids were designed. The amino acid sequence of designed peptides was GXGVP, where X equaled to W, Y, F, D, and T with a combination of hydrophobic, charged and polar units. These peptides were linked to quinazolinones to obtain a new class of compounds with synergistic features. The hybrids displayed antimicrobial activity against Gram-positive and Gram-negative bacteria. In particular, Trp, Tyr, and Phe-containing peptides showed greater antimicrobial potency than the reference standards. Alkyl chain length variations in heterocyclic moiety indicated that hybrids with propyl group were more active than butyl derivatives. Improved results were observed for debenzylated versions of the conjugates compared to their benzylated counterparts. Implementation of the hybrid structures of varying charge, hydrophobicity, and alkyl chain length would be a promising approach to obtaining effective antimicrobial agents. [ABSTRACT FROM AUTHOR]

The emergence of multidrug resistant bacteria has a direct impact on global public health because of the reduced potency of existing antibiotics against pathogens. Hence, there is a pressing need for new drugs with different modes of action that can kill microorganisms. Antimicrobial peptides (AMPs) can be regarded as an alternative tool for this purpose because they are proven to have therapeutic effects with broad-spectrum activities. There are some hurdles in using AMPs as clinical candidates such as toxicity, lack of stability and high budgets required for manufacturing. This can be overcome by developing shorter and more easily accessible AMPs, the so-called Short Anti Microbial Peptides (SAMPs) that contain between two and ten amino acid residues. These are emerging as an attractive class of therapeutic agents with high potential for clinical use and possessing multifunctional activities. In this review we attempted to compile those SAMPs that have exhibited biological properties which are believed to hold promise for the future. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Polymyxins have re-emerged as the last-line therapy for treatment against extremely multi-drug resistant Gram-negative bacteria, which pose a global threat to public health. Colistin is a polymyxin antibiotic which is effective against most Gram-negative bacteria. Herein, we report a facile and convenient synthesis of a colistin analogue. All the Dabs were protected as Boc groups except for Dab4 which was Alloc protected and used for cyclization with Thr10. The choice of Boc over other protecting groups was to enhance the solubility of the peptide. Cyclization in a volatile solvent such as DCM under very mild conditions and precipitation of the peptide using water are additional advantages of this protocol which can potentially be used for bulk production. The colistin analogue revealed good antibacterial activity in comparison to the natural version. [ABSTRACT FROM AUTHOR]

Application of a bromomaleimide core allows for the incorporation of three different peptides. The key reactions of the process are the selective stapling of both thiol- and amino-peptides on two different sites of the core. The thiol-peptide attacks and replaces the bromide whereas the amino-peptide attaches to the ene-position of the core revealing differential and selective reactivity. This platform will have further application in protein chemistry, multidrug presentation and vaccine preparation. [ABSTRACT FROM AUTHOR]

LL37, a human cathelecidin antimicrobial peptide comprising of 37 amino acids has emerged as one of the vital therapeutic peptides associated with a number of biological applications. In this context, we herein report a highly efficient and optimized methodology for the synthesis of LL37 through SPPS assisted by microwave power. Standard conditions employing uronium coupling reagents was unsatisfactory from the 20th amino acid residue onwards. A segmentation approach revealed that the amide bond formation between the Val and Ile was identified as the problematic coupling. It was found that DIC/OxymaPure in conjunction with THF as the solvent gave best results during manual coupling of 20th position Ile and required double coupling as revealed by HPLC and MALDI-TOF MS. In order to verify the synthesis, antibacterial testing was carried out and the results revealed comparable values with that of literature reported. [ABSTRACT FROM AUTHOR]

Wereport on a novel and user-friendly platform based on a bromomaleimidemoiety to obtain branched peptides. The platform is stable for allSPPS conditions. The bromomaleimide core was conjugated to n-copies of thiol–peptide in-solution to obtain two/four/eight-armeddendrimers. Using ‘n’ number of bromomaleimideanalogues, 2nligands were incorporatedat both bromo and ene positions via a thioether bond. This methodhas the advantage of high conversion in a short time, thus enablingeffortless purification and characterization processes. [ABSTRACT FROM AUTHOR]

Noninvasive imaging is a powerful tool for early diagnosis and monitoring of various disease processes, such as infections. An alarming shortage of infection-selective radiopharmaceuticals exists for overcoming the diagnostic limitations with unspecific tracers such as 67/68Ga-citrate or 18F-FDG. We report here TBIA101, an antimicrobial peptide derivative that was conjugated to DOTA and radiolabeled with 68Ga for a subsequent in vitro assessment and in vivo infection imaging using Escherichia coli-bearing mice by targeting bacterial lipopolysaccharides with PET/CT. Following DOTA-conjugation, the compound was verified for its cytotoxic and bacterial binding behaviour and compound stability, followed by 68Gallium-radiolabeling. µPET/CT using 68Ga-DOTA-TBIA101 was employed to detect muscular E. coli-infection in BALB/c mice, as warranted by the in vitro results. 68Ga-DOTA-TBIA101-PET detected E. coli-infected muscle tissue (SUV = 1.3–2.4) > noninfected thighs (P=0.322) > forearm muscles (P=0.092) > background (P=0.021) in the same animal. Normalization of the infected thigh muscle to reference tissue showed a ratio of 3.0 ± 0.8 and a ratio of 2.3 ± 0.6 compared to the identical healthy tissue. The majority of the activity was cleared by renal excretion. The latter findings warrant further preclinical imaging studies of greater depth, as the DOTA-conjugation did not compromise the TBIA101’s capacity as targeting vector. [ABSTRACT FROM AUTHOR]

The primary idea of using immobilized reagents in organic synthetic chemistry is to simplify the downstream process, product workup and isolation, and therefore avoiding timeconsuming and expensive chromatographic separations, which are intrinsic to every synthetic process. Numerous polymer-bounded reagents are commercially available and applicable to almost all kinds of synthetic chemistry conversions. Herein, we have covered all known supported-coupling reagents and bases which have had a great impact in amide/peptide bond formation. These coupling reagents have been used for the activation of a carboxyl moiety; thus generating an active acylating species that is ready to couple with an amine nucleophile liberating the amide/peptide and polymeric support which can be regenerated for reuse. This also addresses a large variety of anchored coupling reagents, additives, and bases that have only been employed in amide/peptide syntheses during the last six decades. [ABSTRACT FROM AUTHOR]

Here we review the strategies for the solid-phase synthesis of peptides starting from the side chain of the C-terminal amino acid. Furthermore, we provide experimental data to support that C-terminal and side-chain syntheses give similar results in terms of purity. However, the stability of the two bonds that anchor the peptide to the polymer may determine the overall yield and this should be considered for the large-scale production of peptides. In addition, resins/linkers which do not subject to side reactions can be preferred for some peptides. [ABSTRACT FROM AUTHOR]

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Review: 150 refs. [ABSTRACT FROM AUTHOR]

Review: 74 refs. [ABSTRACT FROM AUTHOR]