Peptides are fragments of proteins that carry out biological functions. They act as signaling entities via all domains of life and interfere with protein-protein interactions, which are indispensable in bio-processes. Short peptides include fundamental molecular information for a prelude to the symphony of life. They have aroused considerable interest due to their unique features and great promise in innovative bio-therapies. This work focusing on the current state-of-the-art short peptide-based therapeutical developments is the first global review written by researchers from all continents, as a celebration of 100 years of peptide therapeutics since the commencement of insulin therapy in the 1920s. Peptide “drugs” initially played only the role of hormone analogs to balance disorders. Nowadays, they achieve numerous biomedical tasks, can cross membranes, or reach intracellular targets. The role of peptides in bio-processes can hardly be mimicked by other chemical substances. The article is divided into independent sections, which are related to either the progress in short peptide-based theranostics or the problems posing challenge to bio-medicine. In particular, the SWOT analysis of short peptides, their relevance in therapies of diverse diseases, improvements in (bio)synthesis platforms, advanced nano-supramolecular technologies, aptamers, altered peptide ligands and in silico methodologies to overcome peptide limitations, modern smart bio-functional materials, vaccines, and drug/gene-targeted delivery systems are discussed.

Conformational energy computations on a derivative and a homo‐dipeptide of Cα,α‐diethylglycine were performed. In both cases the N‐ and C‐terminal groups are blocked as acetamido and methylamido moieties, respectively. It was found that the Cα,α‐diethylglycine residues are conformationally restricted and that the minimum energy conformation corresponds to the fully extended C5 structure when the NCαC′ bond angle is smaller than 108° (as experimentally observed). The results of the theoretical analysis are in agreement with the crystal‐state structural propensity of the complete series of N‐trifluoroacetylated homo‐peptides of this Cα,α‐dialkylated residue from monomer to pentamer, determined by x‐ray diffraction and also described in this work. Interestingly, for the first time, a crystallographically planar peptide backbone was observed (in the protected tripeptide). A comparison with peptides of Cα,α‐dimethylglycine, Cα‐methyl, Cα‐ethylglycine, and Cα,α‐di‐n‐propylglycine indicates that the fully extended conformation becomes more stable than the helical structures when both amino acid side‐chain Cβ atoms are substituted.

SynopsisThe conformational preferences of the N-trifluoroacetylated homo-peptides of C", "-diethylglycine from monomer to pentamer in chloroform solution were determined by using ir absorption and 'H-nmr. Intramolecular hydrogen bonding was found to be the dominant factor for all NH groups. The likely absence of a conformational transition upon increasing main-chain length, and the remarkable stability to dilution, heating, and addition of perturbing agents, are additional relevant findings of this study. These results are in agreement with those of the fully extended, C,-conformation-forming homo-peptides from the higher homolog C a y "-di-n-propylglycine, but contrast dramatically to those of the homo-peptides from the lower homolog C", "-dimethylglycine, which have been shown to adopt the 3,,-helical structure.

The dormant state known as diapause is widely exploited by insects to circumvent winter and other adverse seasons. For an insect to survive, feed, and reproduce at the appropriate time of year requires fine coordination of the timing of entry into and exit from diapause. One of the hormones that regulates diapause in moths is the 24-aa neuropeptide, diapause hormone (DH). Among members of the Helicoverpa/Heliothis complex of agricultural pests, DH prompts the termination of pupal diapause. Based on the structure of DH, we designed several agonists that are much more active than DH in breaking diapause. One such agonist that we describe also prevents the entry into pupal diapause when administered to larvae that are environmentally programmed for diapause. In addition, we used the unique antagonist development strategy of incorporating a dihydroimidazole ("Jones") trans-Proline mimetic motif into one of our DH agonists, thereby converting the agonist into a DH antagonist that blocks the termination of diapause. These results suggest potential for using such agents or next-generation derivatives for derailing the success of overwintering in pest species.diapause manipulation | peptidomimetics C oordinating active phases of the life cycle with seasons that provide food resources and suitable environmental conditions is crucial for sustaining viable insect populations. Major portions of the year, most notably winters in temperate zones, are unsuitable for continuous development, and most insects have evolved periods of dormancy (diapause), characterized by suppressed metabolism and bolstered stress responses that enhance survival during unfavorable seasons. Short day lengths of late summer commonly trigger the onset of diapause (1, 2), and these environmental signals prompt endocrine responses that directly initiate and eventually terminate the diapause state (3).Desynchronizing an insect pest with its appropriate seasonal diapause could be used as a tool for disrupting pest populations (4). Altering the timing of diapause has the potential to evoke ecological suicide if the insect is forced to be active during a time of year when climatic conditions are adverse or food resources are absent. Blocking entry into diapause in the autumn, breaking out of an overwintering diapause prematurely, or failing to terminate diapause at the appropriate time in the spring all have potential for desynchronizing the temporal distribution of insects. We report here the development of unique agents capable of disrupting the overwintering pupal diapause of the corn earworm, Helicoverpa zea, a member of the Heliothis/Helicoverpa complex, a worldwide group of noteworthy crop pests (5).Our target is diapause hormone (DH). This 24-aa neuropeptide, a pyrokinin in the DH-pheromone biosynthesis activating neuropeptide (PBAN) family, is best known for its action in initiating embryonic diapause in the commercial silkworm, Bombyx mori (6); however, recently, DH was also shown to exert an opposite effect in pupae of the Heliothis/Helicoverpa co...