Peptides bradykinin

Attaching some short peptidic sequences to adamantane makes it possible to design novel antagonists. The bradykinin antagonist, which is used as an anticancer agent, is an example. The adamantane-based peptidic bradykinin analog was utilized in strucmre-activity relationship (SAR) studies on the bradykinin receptors and showed a potent activity in inhibition of bradykinin-induced cytokine release and stimulation of histamine release [142]. 

Meini S, Cucchi P, BeUucci F, et al. Site-directed mutagenesis at the human B2 receptor and molecular modelling to define the pharmacophore of non-peptide bradykinin receptor antagonists. Biochem Pharmacol 2004 67 601-9. 

Chatterjee, C. and Mukhopadhyay, C. (2005) Interaction and structural study of kinin peptide bradykinin and ganglioside monosialylated 1 micelle. Biopolymers 78, 197-205. 

Muscle cells release kallikrein during inflammation causing formation of active kinin peptides (bradykinin and kallidin) from kininogen [65, 66]. Kinins are peptide hormones that produce vasodilation, increase capillary permeability, and cause pain and infiltration of neutrophils. There is a direct correlation between the amount of kinin in plasma or tissues and the degree of inflammation. Vascular dilation causes increased blood flow to infection [67, 68], Bik inhibits formation of kinins and vascular dilation by kallikrein, thereby inhibiting smooth muscle contraction [69-71],... 

Zhou et al. measured by FA the single-component isotherms of two related peptides, bradykinin and kallidin (MW 1060 and 1188, respectively) on a Zorbax SB Ci8 microbore column (Agilent Technologies), using a 20% aqueous solution of ACN (with 0.1% TFA) as the mobile phase [81]. The isotherm data were fitted to the Langmuir, the bi-Langmuir, the Langmuir-Frermdlich and the Toth isotherm... 

Figure 16.19 Comparison of the experimental (s3nnbols) overloaded elution band profiles of a mixture of the closely related peptides bradykinin and kallidin on a Zorbax SB-C18150 x 0.5 mm column eluted with ACN/H2O, 20/80 v/v (+ 0.5% TFA), for a loading factor Ly = 0.29% and the profiles calculated with the ED (solid lines) and the FOR models (dashed lines), (a) Parameters of the FOR model derived from conventional correlations, (b) Dm in the FOR model optimized numerically at 1 x 10 cm /s. Reproduced with permission from D. Zhou, X. Liu, K. Kaczmarski, A. Felinger, G. Guiochon, Biotech. Prog. 19 (2003) 945 (Figure 4.) 2003, American Chemical Society.

Abe et al. reported that the imidazol [l,2-a]pyridine moiety of the basic framework of a class of the non-peptide bradykinin B2 receptor antagonists (11, Figure 15.14) could be successfully replaced by several heterocyclic bioisosteres. Among those, the l-methyl-2-methoxy-l//-benzimidazole, 2-methylquinoxaline and 2-methylquinoline derivatives showed potent B2 binding affinities against both human and guinea pig B2 receptors (Figure 15.14). 

Figure 10.3 shows the IR-LDI mass spectrum of the peptide bradykinin (Mr = 1060.2) desorbed and ionized from the PDMS cover. The bradykinin was loaded into the chip at a concentration of 2.5 mM and injected into the chip channel using a field of 150 Y cm-1 for 9 min. The spectrum is the result of 10 laser shots at 2.95 pm wavelength. The off-line capillary gel microfluidic mass spectra are obtained after electrophoretic transport through a closed chip channel. Operation with a closed channel requires that the cover be removed from the chip prior to analysis. When removing the cover, sections of the gel tended to adhere to the surface of the PDMS. With some amount of care the entire gel lane could be extracted intact from the chip and, in many cases, irradiation of the PDMS cover resulted in the best mass spectra. The base peak... 

Figure 10.6 Upper panel shows a two-dimensional separation contour plot showing the separation of peptides bradykinin, substance p and bombesin on a PMMA chip. The x axis represents m/z values, the y axis represents the separation and readout times and the gray shade shows the ion intensities. The panel below is a representative electropherogram generated by integrating ion intensities from a two-dimensional plot.

A) Angiotensin I Angiotensin II Atrial natriuretic peptide Bradykinin... 

Values of band width Ot (sec) were calculated (as in Tatde vni) for the various runs of Ref. 40). These data are summarized in Table IX, which compares experimental versus predicted values of o,. Table IX shows that five of these seven peptides (bradykinin and possibly lysozyme excepted) give acceptable agreement with the model. The mean R values for each of... 

FIGURE 15.14 Novel class of orally active non-peptide bradykinin B2 receptor antagonists showing valuable examples of imidazo[l,2-a]pytidine analogs. 

An important discovery in the field of peptide synthesis was made by R. Bruce Merrifield (United States 1921-2006) in 1962. He was able to bind an amino acid to a polymer bead via the C-terminus and subsequently synthesized the peptide bradykinin (arg-pro-pro-gly-phe-ser-pro-phe-arg a potent hypotensive agent) by doing the chemical reactions, including the protection and deprotection steps, on a polymer bead. When completed, the nonapeptide was released from the polymer by a simple chemical reaction. This basic approach is now called the Merrifield synthesis and is one of the most important advancements in peptide synthesis. 

Numerous peptides (bradykinin, neurotensin, flbrinopeptide, etc.) Thymopoietin ... 

We chose to investigate the doubly charged peptide bradykinin ([bk+2H] ) as an example of a molecule with a high degree of spectral complexity arising from multiple conformations. Although it has only nine amino acids, part of the molecule is believed to be intrinsically disordered, which should lead to a distribution of gas-phase conformers. Indeed both previous work using FAIMS [168,169] as well as... 

---