MOTILIN (HUMAN, PORCINE)

Description

Motilin was isolated from the duodenojejunal mucosa and found to control the motor activity of the digestive tract. It is a potential therapeutic drug target for improving digestive dysmotility. Motilin was isolated from a side fraction produced during the purification of secretin in 1971 and was found to stimulate contractility in the fundus of the stomach. Complete porcine and human motilin were purified and sequenced in 1973 and 1983 respectively.

General Description

Motilin is a 22-residue polypeptide isolated from the duodenum.Its secretion is stimulated by the presence of acid inthe duodenum. Motilin inhibits gastric motor activity anddelays gastric emptying.

Clinical Use

To date, almost all macrolides have lacked effectiveness as MLN agonists. However, pharmacies have been trying to develop new types of macrolides, such as PF-04548043 (formerly known as KOS-2187), for the treatment of GI motility disorders such as gastroparesis and gastroesophageal reflux disease. Moreover, the new MLNR agonist RQ-00201894 is a promising drug for the treatment of gastroparesis, postoperative ileus, and functional dyspepsia.

Storage

Store at -20°C

Structure and conformation

Motilin is highly conserved across species, and is synthesized as a part of a larger inactive prohormone. Structure-activity studies with analogs and fragments of porcine motilin have shown an N-terminal region, which is considered a physiological and biological active site, and a C-terminal α-helical domain. Human motilin is synthesized as a preprohormone composed of 133 aa residues, each consisting of a 25-aa signal peptide followed by a 22-aa (mature motilin) and a C-terminal motilin-associated peptide (MAP). In the N-terminal region, identical aa sequences exist in human and porcine motilin, but differ from canine motilin at positions 7, 8, 12, 13, and 14 . Chicken MLN also differs from human and porcine sequences by six residues at positions 4, 7–10, and 12, and the binding affinity and pharmacological potency against the chicken MLNR differ from those for mammalian MLN.