(Ala11, D-Leu15)-Orexin B human – Neuroscience Peptides

Orexin B is one of two closely related peptides- the orexins (also known as hypocretins). These small neuropeptides are secreted from orexin-containing neurons, located mainly in the lateral hypothalamus (LH). Orexins function via the binding and activation of two G-protein-coupled receptors (GPCRs)- orexin receptor type 1 (OX1) and 2 (OX2). [Ala(11), D-Leu(15)]orexin-B is a highly potent and selectiveOX2 receptor agonist which can discriminate between the OX1 and OX2 receptors, with a 400-fold selectivity for the OX2 over OX1. [Ala(11), D-Leu(15)]orexin-B is therefore a beneficial tool for addressing the functional roles of OX2. The L-leucine residue at position 11 of orexin B is important for selectivity to OX2 over OX1. L-Alanine substitution at position 11 and D-leucine substitution at positions 15 maintain the potency of orexin-B to OX2, while significantly reducing the potency for OX1. Orexins play several vital roles in a range of physiological activities, including: circadian rhythm- feeding behaviour- energy balance- glucose metabolism- neuroendocrine functions- stress-adaptive responses and reward and addiction. Orexins have also been linked to the pathological processes of neurological diseases such as: narcolepsy- depression- ischemic stroke- drug addiction and Alzheimer’s disease.

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