Disease relevance of cyclopropane

• A novel mycolic acid cyclopropane synthetase is required for cording, persistence, and virulence of Mycobacterium tuberculosis [1].
• We identified a mycobacterial gene, pcaA, that we show is required for cording and mycolic acid cyclopropane ring synthesis in the cell wall of both BCG and M. tuberculosis [1].
• This activity was localized to a single gene (cma1) encoding a protein that was 34% identical to the cyclopropane fatty acid synthase from Escherichia coli [2].
• Calcipotriol (MC903) is a side chain analog of the vitamin D hormone calcitriol, containing a 22-23 double bond, a 24(S)-hydroxyl function, and carbons 25, 26, and 27 incorporated into a cyclopropane ring which has been developed for treating psoriasis [3].
• Cyclopropane-derived peptidomimetics. Design, synthesis, evaluation, and structure of novel HIV-1 protease inhibitors [4].

High impact information on cyclopropane

• Carbocyclic fatty acids in plants: biochemical and molecular genetic characterization of cyclopropane fatty acid synthesis of Sterculiafoetida [5].
• Despite substantial sequence identity, these proteins catalyze highly specific cyclopropane modifications, including proximal modification of the alpha-mycolate (pcaA) and trans-cyclopropane modification (cmaA2) [6].
• This study establishes mmaA2 as a distal cyclopropane synthase of the alpha-mycolates of M. tuberculosis and the first cyclopropane synthase to modify both alpha- and oxygenated mycolates [6].
• 1-Aminocyclopropane-1-carboxylate deaminase catalyzes the cyclopropane ring-opening reaction followed by deamination specifically [7].
• A survey of plant and bacterial genomes for sequences related to SfCPA-FAS indicated that a peptide domain with a putative flavin-binding site is either fused to the methyltransferase domain of the plant protein or is often found encoded by a gene adjacent to a bacterial cyclopropane synthase gene [8].

Chemical compound and disease context of cyclopropane

• Tetramine 10 containing two cyclopropane rings had the lowest systemic toxicity as reflected in animal body weight loss [9].
• Fluorine-19 nuclear magnetic resonance studies of lipid fatty acyl chain order and dynamics in Acholeplasma laidlawii B membranes. A direct comparison of the effects of cis and trans cyclopropane ring and double-bond substituents on orientational order [10].
• Group A contained Campylobacter jejuni (97%) and most C. coli (83%) strains and was characterized by the presence of a 19-carbon cyclopropane fatty acid (19:0 cyc) and 3-hydroxytetradecanoic acid (3-OH-14:0) [11].
• Methyl sterol and cyclopropane fatty acid composition of Methylococcus capsulatus grown at low oxygen tensions [12].
• Infection of E. coli with phage T3 inhibited cyclopropane fatty acid formation over 98%, whereas infection with mutants which lack the phage coded S-adenosylmethionine cleavage enzyme had no effect on cyclopropane fatty acid synthesis [13].

Biological context of cyclopropane

• The gene whose product cyclopropanates the proximal double bond was cloned by homology to a putative cyclopropane synthase identified from the Mycobacterium leprae genome sequencing project [14].
• Independent confirmation of the SEs of a series of substituted cyclopropenes is provided by their dimerization/combination with cyclopropane to form a six-membered ring reference compound [15].
• However, it is also likely that Ser-78 serves as the active site nucleophile that attacks the cyclopropane ring and initiates the fragmentation of ACC, while the conserved Lys-51 is the base required for beta-H abstraction [16].
• A structure-activity relationship study of spirolactones. Contribution of the cyclopropane ring to antimineralocorticoid activity [17].
• Catalytic hydrogenation of 1 leads to consecutive opening of the two cyclopropane rings to give C(2)-bisseco-octahedrane (pentacyclo[6.4.0.0(2,6).0(3,11).0(4,9)]dodecane) 16 as the major product [18].

Anatomical context of cyclopropane

• Purified TDM isolated from a cyclopropane-deficient pcaA mutant was hypoinflammatory for macrophages and induced less severe granulomatous inflammation in mice, demonstrating that the fine structure of this glycolipid was critical to its proinflammatory activity [19].
• Accordingly, as demonstrated in gel filtration experiments, flavohemoglobin is able to bind liposomes obtained from lipid extracts of E. coli membranes and eventually abstract phospholipids containing cis double bonds and/or cyclopropane rings along the acyl chains [20].
• The effects of the enantiomers of (+/-)-CAMP and (+/-)-TAMP [(+/-)-cis- and (+/-)-trans-2-aminomethylcyclopropanecarboxylic acids, respectively], which are cyclopropane analogues of GABA, were tested on GABA(A) and GABA(C) receptors expressed in Xenopus laevis oocytes using two-electrode voltage clamp methods [21].
• We compared peripheral nerve regeneration in adult rats with sciatic nerve gaps of 16 mm after autologous transplantation of GFP-labeled SDSCs into two different types of guides: a synthetic guide, obtained by dip coating with a L-lactide and trimethylene carbonate (PLA-TMC) copolymer and a collagen-based guide [22].
• In biological assays conducted in an AP1 cell line expressing the human NHE-1 isoform, the starting cyclopropane 3a (IC(50) = 3.5 microM) shows inhibitory activity comparable to cariporide (IC(50) = 3.4 microM) [23].

Associations of cyclopropane with other chemical compounds

• Analysis by proton NMR indicates that the mycolic acids of the cmaA2 mutant lack trans-cyclopropane rings but are otherwise intact with respect to cyclopropane and methyl branch content [24].
• The CH2I-I species readily reacts with ethylene to give the cyclopropane product and an I2 product via a one-step reaction with a barrier height of approximately 2.9 kcal/mol [25].
• Oxidation-reduction chemistry of DL-alpha-lipoic acid, propanedithiol, and trimethylene disulfide in aprotic and in aqueous media [26].
• The trimethylene- and biphenylene-bridged cations D(CH(2))(3)D*(+) and D(ph)(2)D*(+) with highly localized charge distributions are prototypical class II systems involving moderately coupled redox centers with H approximately equal to 400 cm(-1) [27].
• These derivatives are characterized by having a fluorine atom at the 2-position on the cyclopropane ring as the N1 substituent and consist of both cis and trans stereoisomers [28].

Gene context of cyclopropane

• It is demonstrated that introduction of appropriate hydrophobic groups at the phenyl ring and a gem-dimethyl group at the cyclopropane ring enhances the NHE-1 inhibitory activity by up to 3 orders of magnitude (compound 7f, IC(50) = 0.003 microM) [23].
• The 3' end of the ribC gene is directly adjacent to the cfa gene, which codes for cyclopropane-fatty-acid synthase [29].
• Our previous studies have shown that 1,1-dichloro-cis-2,3-diaryl cyclopropane (Analog II), a diarylcyclopropyl compound is devoid of estrogenic activity, has a weak binding affinity for the estrogen receptor in the mouse uterine tissue and inhibits the growth of breast cancer cells in culture [30].
• Unlike the parent 1-phenylcyclopropylamine, which is a selective inhibitor of MAO B, both (E)- and (Z)-diastereomers of derivatives having fluorine at the 2-position of the cyclopropane ring were potent and selective irreversible inhibitors of MAO A [31].
• A striking effect was observed for derivatives 3d and 3f, whose 5-HT1A affinity was reinforced by two orders of magnitude with a simultaneous decrease in 5-HT2A binding constants in comparison with trimethylene analogues [32].

Analytical, diagnostic and therapeutic context of cyclopropane

• The combination of cyclic voltammetry, dynamic ESR line broadening, and electronic (NIR) spectroscopy allows the intervalence electron transfer between the redox centers in the mixed-valence system D-br-D*(+) [where br can be an aliphatic trimethylene or an aromatic (poly)phenylene bridge] to be probed quantitatively [27].
• Cyclopropane-containing polyamine analogues are efficient growth inhibitors of a human prostate tumor xenograft in nude mice [9].
• Malignant hyperthermia triggered by cyclopropane during cesarean section [33].
• Involvement of cyclopropane fatty acids in the response of Pseudomonas putida KT2440 to freeze-drying [34].
• Letter: Deposits in cyclopropane flowmeter tubes [35].

References