Machine-Learning-Guided Peptide Drug Discovery: Development of GLP-1 Receptor Agonists with Improved Drug Properties.

Peptide-based drug discovery has surged with the development of peptide hormone-derived analogs for the treatment of diabetes and obesity. Machine learning (ML)-enabled quantitative structure-activity relationship (QSAR) approaches have shown great promise in small molecule drug discovery but have been less successful in peptide drug discovery due to limited data availability. We have developed a peptide drug discovery platform called streaMLine, enabling rigorous design, synthesis, screening, and ML-driven analysis of large peptide libraries.

Evaluation of 1-Triazole-1-[,'-Bis(-butoxycarbonyl)]carboxamidine in Solution-Phase and On-Resin Guanidinylation.

Several guanidines and guanidinylated peptides have substantial potential as therapeutics, but efficient guanidinylation reagents are vital for easy access to these compounds. Presently, pyrazole-1-carboxamidine type reagents are commonly used in the transformations of amines into corresponding guanidines. Here, we report a comparative study of the utility of 1-triazole-1-[,'-bis(-butoxycarbonyl)]carboxamidine, which was synthesized in two steps and readily upscaled to gram amounts.

Perfluoro-tert-butanol for selective on-resin detritylation: a mild alternative to traditionally used methods.

Solid-phase synthesis of cyclic, branched or side-chain-modified peptides typically involves introduction of a residue carrying a temporary side-chain protecting group that undergoes selective on-resin removal. In particular, N-Fmoc-N-(4-methyltriphenylmethyl) (Mtt)-protected lysine and its shorter analogues are commercially available and extensively used in this context. Nevertheless, rapid reliable methods for on-resin removal of Mtt groups in the presence of tert-butyloxycarbonyl (Boc) groups are needed.

Stabilization of Angiotensin-(1-7) by key substitution with a cyclic non-natural amino acid.

Angiotensin-(1-7) [Ang-(1-7)], a heptapeptide hormone of the renin-angiotensin-aldosterone system, is a promising candidate as a treatment for cancer that reflects its anti-proliferative and anti-angiogenic properties. However, the peptide's therapeutic potential is limited by the short half-life and low bioavailability resulting from rapid enzymatic metabolism by peptidases including angiotensin-converting enzyme (ACE) and dipeptidyl peptidase 3 (DPP 3). We report the facile assembly of three novel Ang-(1-7) analogues by solid-phase peptide synthesis which incorporates the cyclic non-natural δ-amino acid ACCA.

Physical Activity Levels Among Adolescent and Young Adult Women and Men with and without Intellectual Disability.

Background: As physical activity can prevent overweight and promote general health, the aim was to investigate the amount of physical activity among adolescent and young adult women and men with intellectual disability (ID), compared to age-matched control groups without intellectual disability. A further aim was to examine whether physical activity level was associated with the body mass index (BMI).

Materials And Methods: Fifty-two adolescent and young adult women and men with intellectual disability and 48 without intellectual disability, between the ages 16 and 20 years, BMIs ranging from 16.

Postural muscle responses and adaptations to backward platform perturbations in young people with and without intellectual disability.

This study examines postural muscle responses to backward perturbations in young people (16-20 years) with and without intellectual disability (ID). The study included 56 young people with ID and 43 age-matched without ID volunteers. The subjects stood on a platform that was moved backwards in a surface translation.

Test-retest reliability, smallest real difference and concurrent validity of six different balance tests on young people with mild to moderate intellectual disability.

Objectives: Some studies have reported that people with intellectual disability may have reduced balance ability compared with the population in general. However, none of these studies involved adolescents, and the reliability and validity of balance tests in this population are not known. The purpose of this study was to examine the reliability of six different balance tests and to investigate their concurrent validity.

Adolescents with intellectual disability have reduced postural balance and muscle performance in trunk and lower limbs compared to peers without intellectual disability.

For adolescent people with ID, falls are more common compared to peers without ID. However, postural balance among this group is not thoroughly investigated. The aim of this study was to compare balance and muscle performance among adolescents aged between 16 and 20 years with a mild to moderate intellectual disability (ID) to age-matched adolescents without ID.