Side reactions of monoaminodicarboxylic acids in peptide synthesis

N-benzyloxycarbonyl-l -homoglutamine was studied to answer the question whether or not there is any tendency for the dehydration of the δ-carboxamide group during activation and coupling. Only a minor conversion to nitrile by-products was found in the activation of the α-carboxyl group and formation of peptide bond with the help of dicyclohexylcarbodiimide. Addition of N-hydroxybenzotriazole to the reacting mixture eliminates the side chain dehydration reaction. The dehydration reaction is also overcome by protection of the side chain carboxamide with the benzyloxycarbonylcarbamoyl substituent.     

Sialic acid concentration in different stages of malignant lymphoma and leukemia in children

Sialic acid concentration in the blood serum of 104 children suffering from leukemia and malignant lymphomas was determined. A significant higher concentration of sialic acid was found at the onset of the disease, compared to the controls. In the group of children suffering from acute lymphoblastic leukemia a dependence was noted between the stage of the disease and the concentration of sialic acid in the serum. The high concentration of sialic acid at the onset of the disease, although decreasing during treatment, rose again during relapses of the disease. It seems that determination of sialic acid concentration may be useful in monitoring treatment.     

High-performance liquid chromatography of epimeric N-protected peptide acids and esters for assessing racemization

The separations by reversed phase high-performance liquid chromatography on a μBondapak-C₁₈ column of 53 epimeric N-substituted di-, tri- and tetrapeptide acids and esters have been attempted, with success in three quarters of the cases. Substituents include acetyl, benzoyl, benzyloxycarbonyl, tert.-butoxycarbonyl and 9-fluorenylmethoxycarbonyl. The series N-benzyloxycarbonylglycyl-Xxx-valine ethyl ester with Xxx = alanyl, valyl, leucyl and phenylalanyl, is recommended for use in studies on racemization. Results on racemization attending the coupling of an amino acid ester as compared with a di- and tripeptide ester vary with the coupling method.     

The Treatment of Soman Poisoning and its Perspectives

Soman is a highly toxic organophosphorus chemical warfare nerveagent which is characterized by (1) extremely rapid ageing ofthe phosphonylated enzyme, (2) poor reactivation of inhibitedAChE due to a steric factor, (3) pronounced CNS effects, and(4) tentative direct toxic biochemical effects. By studies ofSoman and its thiocholine-like analog (which yield the sametype of phosphonylated enzyme), it has been established that(1) the steric factor is at least as responsible as ageing inthe failure of oximes to reactivate effectively AChE inhibitedby Soman, (2) that its dealkylation is catalyzed by the anionicsite of the enzyme, and (3) that the velocity of reactivationand ageing of AChE is dependent on the orientation of the phosphonylgroup at the enzyme surface. It has been found that PiMeP-CI(O-pinacolyl methylphosphonochloridate) may serve as a goodmodel in the evaluation of Soman toxicity and in the selectionof adequate oximes in the treatment of its poisoning. The oppositeeffects of TMB-4 and HI-6, as group representatives, on PiMeP-CItoxicity in mice (strong potentiation by TMB-4 and antagonismby HI-6) were mainly ascribed to the rates of decompositionof their corresponding O-pinacolyl methylphosphonylated productsformed in vivo. They are considered to be slow with potentiatorsand instantaneous with antagonists, respectively. This assumptionwas confirmed by the finding that the most powerful oximes inSoman poisoned mice were HI-6, HGG-42 and BDB-27, which, contraryto TMB-4, possess an oxime group in position 2 and the CH2-O-CH2linking chain. The remarkable influence of diazepam and sodiumn-dipropylacetate on the survival time in Soman poisoned ratstreated by atropine and bis-pyridinium oximes points to theirantagonistic action at the biochemical level (decrease of elevatedcGMP in CNS), not possessed by atropine. Essential antidotesin experimental treatment of Soman poisoning today are the powerfulreactivators of Soman-inhibited AChE (e.g. HI-6, HGG-42 andBDB-27) and atropine. The treatment may be further improvedby the use of symptomatic agents capable of counteracting biochemicalchanges in Soman poisoning not antagonized by atropine (e.g.diazepam), and theoretically for now, by retardation of ageingand by overcoming steric disturbances.     

DEVELOPMENT OF CORTICAL AFFERENTS AND CORTICO-TECTAL EFFERENTS OF THE MAMMALIAN (RAT) PRIMARY VISUAL CORTEX

At the time when the fibres from the striate cortex (area 17) begin to innervate the superficial layers of the superior coliiculus of the young rat (postnatal days 4 and 5) a high degree of specificity in the organization of this newly formed cortico-tectal projection is already apparent. Thus, in young rats, as in adult mammals of virtually all species studied so far, the somata of cortico-tectal neurones are confined to lamina V of the ipsilateral cortex. However, this high degree of laminar (radial) specificity in young animals is accompanied by a substantial degree of exuberance as indicated by a tangential distribution of the cortico-tectal cells which is wider than that in the adult. The exuberant projections are pruned during the second postnatal week.
The cortico-cortical associational and commissural fibres start to enter the grey matter of the rat striate cortex after postnatal day 7. Again a high degree of specificity in the laminar distribution of those newly established projections is apparent. However, the cortico-cortical projection, at the time when cortico-cortical fibres enter the cortical laminae, is clearly exuberant since the tangential spread of cortical cells projecting to the striate cortex is wider than that in the adult. Pruning of these excessive projections takes place some time after postnatal day 14.
It is believed that understanding the mechanism(s) underlying the development of connections of the rat visual cortex might be of general importance in understanding developmental abnormalities in the pattern of interconnections of the visual cortices of other mammalian orders.