Vasopressin, lysine

Lysine vasopressin is marketed in nasal spray form as an antidiuretic under the trademark Diapid (Sando2). 

In this work we will focus on the use of the cubic phase as a delivery system for oligopeptides - Desmopressin, Lysine Vasopressin, Somatostatin and the Renin inhibitor H214/03. The amino acid sequences of these peptides are given in Table I. The work focuses on the cubic phase as a subcutaneous or intramuscular depot for extended release of peptide drugs, and as a vehicle for peptide uptake in the Gl-tract. Several examples of how the peptide drugs interact with this lipid-water system will be given in terms of phase behaviour, peptide self-diffusion, in vitro and in vivo release kinetics, and the ability of the cubic phase to protect peptides from enzymatic degradation in vitro. Part of this work has been described elsewhere (4-6). 

In vitro Release of Desmopressin and Lysine Vasopressin. The release experiments were carried out in triplicate according to the USP paddle method (100 rpm, 37 C, 500 mL water). Appropriate amounts of the cubic phase (typically 100 mg) were weighed in small cups (depth=2 mm, diameter=8 mm) drilled non-... 

The Maillard reaction is likely to take on additional significance with the introduction of many new protein and peptide pharmaceuticals. For example, Tarelli et al. have demonstrated that lysine vasopressin undergoes rapid glycation in the presence of reducing sugars in both aqueous and solid formulations and that the N-terminal adduct can form rapidly even at — 20°C [52], A textbook that deals with the consequences for the chemical and life sciences of the Maillard reaction has been published [53]. 

ADH, a nonapeptide, released from the posterior pituitary gland promotes re-absorption of water in the kidney. This response is mediated by vasopressin receptors of the V2 subtype. ADH enhances the permeability of collecting duct epithelium for water (but not for electrolytes). As a result, water is drawn from urine into the hyperosmolar inter-stitium of the medulla. Nicotine augments (p. 110) and ethanol decreases ADH release. At concentrations above those required for antidiuresis, ADH stimulates smooth musculature, including that of blood vessels ( vasopressin ). The latter response is mediated by receptors of the Vi subtype. Blood pressure rises coronary vasoconstriction can precipitate angina pectoris. Lypres-sin (8-L-lysine vasopressin) acts like ADH. Other derivatives may display only one of the two actions. 

Vasopressin occurs in two variations arginine-vasopressin (AVP) and lysine-vasopressin (LVP), in which Arg is replaced by Lys. The conformation of these hormones is almost identical to that of oxytocin, except that the terminal tail is con-formationally free and not held by the ring. The physiological role of the vasopressins is the regulation of water reabsorption in the renal tubules (i.e., an antidiuretic action). In high doses, they promote the contraction of arterioles and capillaries and an increase in blood pressure hence the name of these hormones. Because of their very similar structures, OT and VP overlap in a number of effects. 

During the past decade, vasopressin has proved beneficial in the treatment of vasodilatory shock states, at least in part by virtue of its Vi agonist activity. Terlipressin (triglycyl lysine vasopressin), a synthetic vasopressin analog that is converted to lysine vasopressin in the body, is also effective. It may have advantages over vasopressin because it is more selective for Vi receptors and has a longer half-life. 

Table 5.31. 13C Chemical Shifts (<5C in ppm) of Oxytocin, Arginine Vasotocin, Arginine, and Lysine Vasopressin in D20 [833],...

C Atom Oxytocin Arginine vasotocin Arginine vasopressin Lysine vasopressin... 

Increasing 7[ values in going from the a to the [S to the y carbons of glutamine indicate segmental motion in the side chains of Glu, which is stronger in oxytocin compared to lysine vasopressin. 

Segmental motion of the side chain of lysine in lysine vasopressin is assumed for the same reasons as discussed in 2. for glutamine. According to the 7[ values a similar... 

The mobility of the acyclic terminal tripeptide in lysine vasopressin is larger compared to that in oxytocin, which is coincident with a model suggested from H NMR studies [856]. 

Terlipressin, a long-acting vasopressin analogue, is metabolized to the active drug lysine vasopressin. The use of terlipressin to treat acute variceal bleeding has been reviewed (2,3). 

Lypressin (8-L-lysine-vasopressin) acts like AVP. Other derivatives may display only one of the two actions. 

Phenolic esters are obtained similarly. The presence of a nitro group in the aromatic nucleus and the use of pyridine as solvent facilitates the reaction. This reaction is recommended for the characterization of phenols. 2,4,5-Trichlorophenyl-, pentachlorophenyl-, 4-nitrophenyl- and thiophenyl esters of N-acylamino acids are prepared in this manner. These aromatic esters are used in the stepwise lengthening of peptides, du Vigneaud and coworkers synthesized lysine vasopressin from a nonapeptide which they prepared stepwise using the nitrophenyl ester method. Room temperature esterification of dicarboxylic acids and diphenols are also carbodiimide mediated using the 1 1 complex derived from DMAP and p-toluenesulfonic acid as catalyst Methacrylic acid is also esterified with phenols using carbodiimides and DMPA to mediate the reaction. ... 

It was found that the molecular tumbling of the qrdic dipeptides became dower as the bulkiness increased, 1. e, in the above order, and that the caibcm atoms included in proline pyrrolidine rings of flexible linear dipeptides have a hi mobility while those of rigid cydic dipeptides have a low mobility. The relaxation time has also been determined from NMR spectroscopy of gramiddin S (65), oxytodn (69), and lysine vasopressin (69). 

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