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Marine Fungi-Derived Secondary Metabolites: Potential as Future Drugs for Health Care
Published in Hafiz Ansar Rasul Suleria, Megh R. Goyal, Health Benefits of Secondary Phytocompounds from Plant and Marine Sources, 2021
Syed Shams Ul Hassan, Hui-Zi Jin, Abdur Rauf, Saud Bawazeer, Hafiz Ansar Rasul Suleria
The cyclic tetrapeptide penicopeptide A (image 16 in Figure 8.1) was isolated from the culture broth of the endophytic fungus (Penicillium commune) that was derived from the leaves of mangrove plant (Vitis vinifera) in Gansu province of China. The compound penicopeptide A was examined against 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme; and it exhibited potent inhibitory activity against human 11β-HSD1, with an IC50 value of 9.07 ± 0.61μM. From these studies, it has been revealed that the novel structure of the compound penicopeptide A with its potent inhibitory activities against 11β-HSD1 opens the gates for more 11β-HSD1 inhibitors from marine natural products [54].
Diseases of the Nervous System
Published in George Feuer, Felix A. de la Iglesia, Molecular Biochemistry of Human Disease, 2020
George Feuer, Felix A. de la Iglesia
There are reports suggesting that various fragments from the pituitary hormone, such as β-lipotropin, elicit sedative action on the central nervous system and may be involved in the process of sleep. Methionine-enkephalin, a tetrapeptide, and leucine-enkephalin, a related pentapeptide, have transient analgesic effects. Larger fragments of the hormone α-endorphin containing 16 and β-endorphin containing 21 amino acids exert potent long-lasting analgesia when injected to various experimental animals. These observations may imply that peptide fragments are important neuromodulators of the central nervous system, and their function is connected with sleep mechanisms. The behavioural action of these peptides shows striking similarity to those of some central nervous system neuropeptides and may be involved in psychopathological conditions which can be controlled by neuroleptic drugs. The changes in neuropeptides may be associated with alterations of the enzyme activity responsible for the production of these peptides from the intact hormone.
The Renin-Angiotensin System
Published in Austin E. Doyle, Frederick A. O. Mendelsohn, Trefor O. Morgan, Pharmacological and Therapeutic Aspects of Hypertension, 2020
A range of synthetic peptides containing the sequence Leu-Leu were found to be inhibitors of the reaction of rabbit renin and substrate.606,607 Those peptides which were active had Leu-Leu at the amino-terminus, the amino-terminal Leu was in the L configuration, and Tyr or Phe occurred at the C-terminus. Examples of active inhibitors were the methyl or ethyl esters of Leu-Leu-Val-Tyr or Leu-Leu-Val-Phe. These compounds were competitive inhibitors producing 50% inhibition of renin at approximately 2 mg/mℓ and were of comparable activity to the octapeptide, Pro-Phe-His-Leu-Val-Tyr-Ser. The methyl esters of these two tetrapeptides (Leu-Leu-Val-Tyr-Och3 and Leu-Leu-Val-Phe-OCH3) and the tripeptide (Leu-Leu-Val-OCH3) were found to be inhibitors of the reaction od hog renin with a synthetic 3H-labeled tetradecapeptide substrate, of human renin with the synthetic substrate, and of human renin with plasma substrate.38 The tetrapeptides were more active than the tripeptide, and all were more effective in inhibiting the action of human rather than hog renin acting on the synthetic substrate (Table 6). The tetrapeptide, Leu-Leu-Val-Tyr-OCH3, was shown to be a classical competitive inhibitor, but was not cleaved by renin.
Discovery of dual S-RBD/NRP1-targeting peptides: structure-based virtual screening, synthesis, biological evaluation, and molecular dynamics simulation studies
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Chunfang Hu, Ting Guo, Yunting Zou, Junyi Gao, Yi Gao, Miaomiao Niu, Yang Xia, Xiaozhou Shen, Jindong Li
The crystal structure of the b1 domain of NRP1 (NRP1-BD) was obtained from PDB (PDB ID: 7JJC) and preprocessed via Prepare Protein tool. The virtual library containing 24 000 peptides was self-constructed using the QuaSAR-CombiGen module of MOE. This module created a random peptide by linking nonapeptide fragments, heptapeptide fragments, dodecapeptide fragments, and tetrapeptide fragments; see the reported article for more details34. The converting of each peptide structure from 2D to 3D was achieved by the use of the Energy Minimisation algorithm. Based on the generated pharmacophore model of S-RBD, a pharmacophore-based docking simulation was conducted to identify S-RBD-targeting peptides by the Docking module of MOE. Key residues on the binding surface of S-RBD were selected as a binding site. The pharmacophore-base docking algorithm served to dock peptides into the S-RBD binding site. The binding free energy was calculated by the dG docking scoring. The selected peptides with docking scores lower than −13.5 kcal/mol subsequently docked into the NRP1-BD active site with the triangle matcher algorithm. Finally, according to the dG docking scores, the top five peptides were selected for in vitro biological testing.
Advances in molecular therapies for targeting pathophysiology in spinal cord injury
Published in Expert Opinion on Therapeutic Targets, 2023
Ha Neui Kim, Madeline R. McCrea, Shuxin Li
Local injection of peptide amphiphile supramolecular polymers into lesioned spinal cord could stimulate remarkable vascular growth, axonal regeneration, myelination, survival of motor neurons, reduced gliosis, and functional recovery [109]. This study reported the new synthetic nanoscale polymers that contain peptides to activate integrin β-1 and basic FGF2 receptors. These biomaterials preserve biological signals of two receptors at the same extent but slightly mutate the tetrapeptide sequence of targeted domains, thus exhibiting great therapeutic potential for severe CNS injury. Treatments with epothilones, the natural compounds that could stabilize microtubules, increased axon regrowth and locomotor recovery of hindlimbs in SCI rats, and a combination of epothilone B with rehabilitation showed complementary effects on functional recovery [110].
Acute myocardial infarction therapy using calycosin and tanshinone co-loaded; mitochondrion-targeted tetrapeptide and cyclic arginyl-glycyl-aspartic acid peptide co-modified lipid-polymer hybrid nano-system: preparation, characterization, and anti myocardial infarction activity assessment
Published in Drug Delivery, 2022
Jieke Yan, Jing Guo, Yuzhen Wang, Xiaowei Xing, Xuguang Zhang, Guanghao Zhang, Zhaoqiang Dong
Mitochondria is a major intracellular organelle and an important drug intracellular target, which has functional roles in cellular metabolism, cell proliferation and death (Dhanasekaran et al., 2020). A mitochondrion-targeted tetrapeptide, MTP-131 (also called elamipretide, SS-31, or Bendavia), H-D-Arg-Dmt-Lys-Phe-NH2, is a water-soluble tetra-peptide (Miyamoto et al., 2020). It binds with high affinity to cardiolipin (CL), an anionic phospholipid expressed on the inner mitochondrial membrane that is required for cristae formation (Zhao et al., 2004; Birk et al., 2013). The mitochondria-targeted nanoparticles were developed to penetrate through the mitochondrial membrane, driving the molecules to accumulate within the mitochondria (Li et al., 2019). Hence, mitochondria-targeted drug delivery systems have achieved promising anticancer effects in cancer chemotherapy. Cyclic arginyl-glycyl-aspartic acid (RGD) peptide has been explored by our group as an αvβ3 integrin receptor-specific targeting moiety for the targeted delivery of nanoparticles to MI site, in which αvβ3 integrin is highly expressed (Dong et al., 2017).