Abstract

It has been shown that the Oral administration for 6 days of 100 mg/kg MMK-1, of an agonist peptide selective for the FPRL1 receptor, suppressed alopecia induced by the anticancer drug etoposide in neonatal rats. However, the anti-alopecia effect of orally administered MMK-1 was inhibited by indomethacin, an inhibitor of cyclooxygenase (COX), or AH-23848B, an antagonist of the EP4 receptor for prostaglandin (PG) E2, suggesting involvement of PGE2 release and the EP4 receptor in the oral MMK-1 anti-alopecia mechanism. The anti-alopecia effect of orally administered MMK-1 was also blocked by an inhibitor of nuclear factor-kappaB (NF-kappaB), pyrrolidine dithiocarbamate, suggesting that the oral anti-alopecia effect of MMK-1 may be mediated by activation of NF-kappaB. These results suggested that MMK-1 bound to FPRL1 receptor might suppress etoposide-induced apoptosis of hair follicle cells and alopecia by way of PGE2 release and NF-kappaB activation. Previously, it has also been found that an intraperitoneally administered chemotactic peptide, N-formyl-Met-Leu-Phe (fMLP), and MMK-1, a selective agonist of formyl peptide receptor-like 1 (FPRL1) receptor, the low affinity subtype of the fMLP receptor, prevented the alopecia in neonatal rats induced by the anticancer agent etoposide. The anti-alopecia effect of fMLP was not inhibited at all by Boc-FLFLF, a selective antagonist of formylpeptide receptor (FPR), which is the high affinity subtype of the receptor, but it was partly inhibited by Trp-Arg-Trp-Trp-Trp-Trp-NH(2) (WRW(4)), an antagonist of FPRL1 receptor. The anti-alopecia effects of fMLP and MMK-1 were also inhibited by Lys-D-Pro-Thr (K(D)PT) and pyrrolidine dithiocarbamate, which are inhibitors of interleukin-1 (IL-1) and nuclear factor-kappaB (NF-kappaB) respectively. Computational methods utilizing the structural and functional information help to understand specific molecular recognition events between the target biomolecule and candidate hits and make it possible to design improved lead molecules for the target. The condition of a quantum Lyapunov-based control which can be well used in a closed quantum system is that the method can make the system convergent but not just stable. In the convergence study of the quantum Lyapunov control, two situations are classified: nondegenerate cases and degenerate cases. For these two situations, respectively, in this paper the target state is divided into four categories: the eigenstate, the mixed state which commutes with the internal Hamiltonian, the superposition state, and the mixed state which does not commute with the internal Hamiltonian. For these four categories, the quantum Lyapunov control methods for the closed quantum systems are summarized and analyzed. Particularly, the convergence of the control system to the different target states is reviewed, and how to make the convergence conditions be satisfied is summarized and analyzed. Here we represents a massive on-going scientific endeavor to provide a freely accessible state of the art software suite for protein and DNA targeted lead molecule of a Mechanistic in silico molecular recognized approach for the ligand based generation of a dual N-formyl-Met-Leu-Phe (fMLP), and MMK-1peptide mimetic agonists formyl-peptide hyper-agonist interactive receptors against chemotherapy-induced alopecia.

Keywords

mechanistic; in silico; molecular; recognized approach; ligand based; dual N-formyl-Met-Leu-Phe (fMLP), MMK-1peptide mimetic; hyper-agonist; fMLP targeted receptor; PGE2 EP4 pathway; chemotherapy-induced alopecia;