Reduction of virginiamycin S with sodium borohydride produces allo- & normal-dihydro-virginiamycin S. Reduction of the tosylhydrazone of virginiamycin S with sodium cyanoborohydride affords deoxyvirginiamycin S. These compounds are less active than virginiamycin S. Like virginiamycin S they enhance the activity of virginiamycin M1.
Virginiae butanolides (VBs), which are among the butyrolactone autoregulators of Streptomyces species, act as a primary signal in Streptomyces virginiae to trigger virginiamycin biosynthesis & possess a specific binding protein, BarA. To clarify the in vivo function of BarA in the VB-mediated signal pathway that leads to virginiamycin biosynthesis, two barA mutant strains (strains NH1 & NH2) were created by homologous recombination. In strain NH1, an internal 99-bp EcoT14I fragment of barA was deleted, resulting in an in-frame deletion of 33 amino acid residues, including the second helix of the probable helix-turn-helix DNA-binding motif. With the same growth rate as wild-type S. virginiae on both solid & liquid media, strain NH1 showed no apparent changes in its morphological behavior, indicating that the VB-BarA pathway does not participate in morphological control in S. virginiae. In contrast, virginiamycin production started 6 hr earlier in strain NH1 than in the wild-type strain, demonstrating for the first time that BarA is actively engaged in the control of virginiamycin production & implying that BarA acts as a repressor in virginiamycin biosynthesis. In strain NH2, an internal EcoNI-SmaI fragment of barA was replaced with a divergently oriented neomycin resistance gene cassette, resulting in the C-terminally truncated BarA retaining the intact helix-turn-helix motif. In strain NH2 & in a plasmid-integrated strain containing both intact & mutated barA genes, virginiamycin production was abolished irrespective of the presence of VB, suggesting that the mutated BarA retaining the intact DNA-binding motif was dominant over the wild-type BarA. These results further support the hypothesis that BarA works as a repressor in virginiamycin production & suggests that the helix-turn-helix motif is essential to its function. In strain NH1, VB production was also abolished, thus indicating that BarA is a pleiotropic regulatory protein controlling not only virginiamycin production but also autoregulator biosynthesis.
Previous findings suggest the location of the central loop of domain V of 23S rRNA within the peptidyltransferase domain of ribosomes. This enzymatic activity is inhibited by some antibiotics, including type A (virginiamycin M or VM) & type B (virginiamycin S or VS) synergimycins, antibiotics endowed with a synergistic action in vivo. In the present work, the ability of VM & VS to modify the accessibility of 23S rRNA bases within ribosomes to chemical reagents has been explored. VM afforded a protection of rRNA bases A2037, A2042, G2049 & C2050. Moreover, when ribosomes were incubated with the two virginiamycin components, the base A2062, which was protected by VS alone, became accessible to dimethyl sulphate (DMS). Modified reactivity to chemical reagents of different rRNA bases located either in the central loop of domain V or in its proximity furnishes experimental evidence for conformational ribosome alterations induced by VM binding
来源:Hazardous Substances Data Bank (HSDB)
毒理性
副作用
皮肤致敏剂 - 一种可以诱导皮肤产生过敏反应的制剂。
Skin Sensitizer - An agent that can induce an allergic reaction in the skin.
来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases
Emergency and supportive measures: Maintain an open airway and assist ventilation if necessary. Treat coma, seizures, hypotension, anaphylaxis, and hemolysis if they occur. Replace fluid losses resulting from gastroenteritis with intravenous crystalloids. /Antibacterial agents/
来源:Hazardous Substances Data Bank (HSDB)
毒理性
解毒与急救
去污：如果条件适当，口服活性炭。如果可以迅速给予活性炭，在小到中等摄入量后不需要洗胃。/抗菌剂/
Decontamination: Administer activated charcoal orally if conditions are appropriate. Gastric lavage is not necessary after small to moderate ingestions if activated charcoal can be given promptly. /Antibacterial agents/
Enhanced elimination: Most antibiotics are excreted unchanged in the urine, so maintenance of adequate urine flow is important. The role of forced diuresis is unclear. Hemodialysis is not usually indicated, except perhaps in patients with renal dysfunction and a high level of a toxic agent. /Antibacterial agents/
/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/
The results of residue determinations of the growth promotors carbadox, tylosin, & virginiamycin in kidney, liver, & muscle from pigs in feeding experiments are described as well as the analytical methods used. Residues of the carbadox metabolite quinoxaline-2-carboxylic acid were found in liver from pigs fed 20 mg/kg in the diet with a withdrawal time of 30 days. No residues were detected in muscle with zero withdrawal time. The limit of determination was 0.01 mg/kg for both tissues. No residues of virginiamycin & tylosin were found in pigs fed 50 & 40 mg/kg, respectively, in the diet, even with zero withdrawal time. Residues of tylosin of 0.06 mg/kg & below were detected in liver & kidney from pigs fed 200 or 400 mg/kg & slaughtered within 3 h after the last feeding.
[EN] DERIVATIVES OF AMANITA TOXINS AND THEIR CONJUGATION TO A CELL BINDING MOLECULE<br/>[FR] DÉRIVÉS DE TOXINES D'AMANITES ET LEUR CONJUGAISON À UNE MOLÉCULE DE LIAISON CELLULAIRE
申请人：HANGZHOU DAC BIOTECH CO LTD
公开号：WO2017046658A1
公开（公告）日：2017-03-23
Derivatives of Amernita toxins of Formula (I), wherein, formula (a) R 1, R 2, R 3, R 4, R 5, R 6, R 7, R 8, R 9, R 10, X, L, m, n and Q are defined herein. The preparation of the derivatives. The therapeutic use of the derivatives in the targeted treatment of cancers, autoimmune disorders, and infectious diseases.
[EN] A CONJUGATE OF A CYTOTOXIC AGENT TO A CELL BINDING MOLECULE WITH BRANCHED LINKERS<br/>[FR] CONJUGUÉ D'UN AGENT CYTOTOXIQUE À UNE MOLÉCULE DE LIAISON CELLULAIRE AVEC DES LIEURS RAMIFIÉS
申请人：HANGZHOU DAC BIOTECH CO LTD
公开号：WO2020257998A1
公开（公告）日：2020-12-30
Provided is a conjugation of cytotoxic drug to a cell-binding molecule with a side-chain linker. It provides side-chain linkage methods of making a conjugate of a cytotoxic molecule to a cell-binding ligand, as well as methods of using the conjugate in targeted treatment of cancer, infection and immunological disorders.
[EN] CROSS-LINKED PYRROLOBENZODIAZEPINE DIMER (PBD) DERIVATIVE AND ITS CONJUGATES<br/>[FR] DÉRIVÉ DE DIMÈRE DE PYRROLOBENZODIAZÉPINE RÉTICULÉ (PBD) ET SES CONJUGUÉS
申请人：HANGZHOU DAC BIOTECH CO LTD
公开号：WO2020006722A1
公开（公告）日：2020-01-09
A novel cross-linked cytotoxic agents, pyrrolobenzo-diazepine dimer (PBD) derivatives, and their conjugates to a cell-binding molecule, a method for preparation of the conjugates and the therapeutic use of the conjugates.
Kappa agonist compounds and pharmaceutical formulations thereof
申请人：——
公开号：US20030144272A1
公开（公告）日：2003-07-31
Compounds having kappa opioid agonist activity, compositions containing them and method of using them as analgesics are provided.
The compounds of formulae I, II, IIA, III, IIIA, IIIB, IIIB-i, IV and IVA have the structure:
1
2
wherein
R
1
, R
2
, R
3
, R
4
; and
X, X
4
, X
5
, X
7
, X
9
;
Y, Z and n are as described in the specification.
[EN] MACROCYCLIZATION OF PEPTIDOMIMETICS<br/>[FR] MACROCYCLISATION DE PEPTIDOMIMÉTIQUES
申请人：UNIV WARWICK
公开号：WO2019186174A1
公开（公告）日：2019-10-03
The invention provides an improved method of macrocyclization of peptidomimetics, as measured by isolated yields and product distribution, which comprises substitution of one or more of the backbone amide C=O bonds with a turn-inducing motif. The method is general with enhancements seen across a range of ring sizes (e.g. tri-, tetra-, penta- and hexapeptides). Specifically, the invention provides a peptidomimetic macrocycle comprising a carbonyl bioisosteric turn-inducing element having the structure: (I) wherein X is a heteroatom; and wherein R1 to R6 are each independently selected from alkyl, aryl, heteroaryl and H.
