An approach to sequence-specific antibody proteases

We describe here a novel strategy for the isolation of antibodies with sequence-specific protease activity: the synthesis of dipeptide haptens in which the targeted peptide bond has been replaced by a ring-strained or torsionally strained hydroxyethylene transition-state analog. Thus, the analogs mimic both a peptide bond in a distorted, reactive conformation and the transition state for peptide bond hydrolysis. In order to obtain sequence-specific antibody proteases, these analogs have been flanked with additional amino acid residues in preparation for immunization. In particular, we have synthesized peptides containing analogs such as 2-cis-amino-3-cis-hydroxycyclobutane carboxylic acid andendo-(3-amino-2-hydroxy)bicyclo[2.2.1]heptane-7-anti-carboxylic acid. We have also prepared a series of peptide derivatives containing analogs, such as 2-[3-amino-2-oxo-1-azetidinyl]-3-methylbutanoic acid, in which the targeted peptide bond has been incorporated into a β-lactam ring. Since the “peptide bond” has been left intact, these species mimic only a distorted ground state. At present, antibodies are being elicited against a number of the above peptide derivatives.     

Synthesis of pyrrolo[3,2-b]benzofurans and pyrrolo[3,2-b]naphthofurans via addition of a silyloxypyrrole to activated quinones

The uncatalyzed reaction of N-(tert-butoxycarbonyl)-2-tert-butyldimethylsilyloxypyrrole 3 with 1,4-quinones bearing an electron withdrawing group at C-2 has been studied. Use of 1,4-quinones 4, 5 bearing an ester group at C-2 provided an efficient synthesis of the respective pyrrolidinobenzofuran adduct 9 or pyrrolidinonaphthofuran adduct 10 whereas use of 1,4-quinones 6, 7 and 8 bearing an acetyl group at C-2 afforded silyloxypyrroles 11, 12 and 13 resulting from direct electrophilic substitution of the silyloxypyrrole by the electrophilic quinone. Addition of Eu(fod)₃ to the reaction of 2-acetyl-1,4-naphthoquinone 7 and 3-acetyl-5-methoxy-1,4-naphthoquinone 8 with N-(tert-butoxycarbonyl)-2-tert-butyldimethylsilyloxypyrrole 3 provided a method for obtaining the pyrrolidinonaphthofuran adducts 14 and 15 together with silyloxypyrroles 12 and 13. Oxidative rearrangement of pyrrolidinonaphthofuran adduct 15 to pyrrolidino pyranonaphthoquinone 16 using ceric ammonium nitrate in acetonitrile provided a novel approach for the synthesis of an aza-analogue of the pyranonaphthoquinone antibiotic kalafungin.     

On functorial decompositions of self-smash products

We give a decomposition formula for n-fold self smash of a two-cell suspension X localized at 2. The mod 2 homology of each factor in the decomposition is explicitly given as a module over the Steenrod algebra and in the case where X is formed by suspending one of P²,P²,P² or P², this is a complete decomposition into indecomposable pieces. The method has consequences in the modular representation theory of the symmetric group where it leads to a computation of the submatrix for the decomposition matrix of the group algebra /2[S_n] which correspond to partitions of length 2. In particular this yields a derivation of the explicit formula due to Erdmann which gives the multiplicities in the decomposition of /2[S_n] of the indecomposable projective modules which correspond to those partitions.     

On the ring of invariants ofF_{2^n }^*

In [1] the first and last authors studied a decomposition ofH ^*(R P ^∞×…×R P ^∞;F ₂) into modules over the Steenrod algebra obtained from an action of the cyclic group . Here a minimal set of generators for the ring of invariants is characterized and counted by analyzing the associated ring of Laurent polynomials. A structure theorem for the ring of invariant Laurent polynomials is given and a ‘destabilisation cancels localisation’ theorem is obtained. The authors gratefully acknowledge the support of NSERC. 1980 Mathematics Subject classification, 13F20, 55. Keywords: Invariant theory, Steenrod algebra.     

FTIR microscopy of biological cells and tissue: data analysis using resonant Mie scattering (RMieS) EMSC algorithm

Transmission and transflection infrared microscopy of biological cells and tissue suffer from significant baseline distortions due to scattering effects, predominantly resonant Mie scattering (RMieS). This scattering can also distort peak shapes and apparent peak positions making interpretation difficult and often unreliable. A correction algorithm, the resonant Mie scattering extended multiplicative signal correction (RMieS-EMSC), has been developed that can be used to remove these distortions. The correction algorithm has two key user defined parameters that influence the accuracy of the correction. The first is the number of iterations used to obtain the best outcome. The second is the choice of the initial reference spectrum required for the fitting procedure. The choice of these parameters influences computational time. This is not a major concern when correcting individual spectra or small data sets of a few hundred spectra but becomes much more significant when correcting spectra from infrared images obtained using large focal plane array detectors which may contain tens of thousands of spectra. In this paper we show that, classification of images from tissue can be achieved easily with a few (<10) iterations but a reliable interpretation of the biochemical differences between classes could require more iterations. Regarding the choice of reference spectrum, it is apparent that the more similar it is to the pure absorption spectrum of the sample, the fewer iterations required to obtain an accurate corrected spectrum. Importantly however, we show that using three different non-ideal reference spectra, the same unique correction solution can be obtained.     

Homology and some homotopy decompositions for the James filtration on spheres

The filtrations on the James construction on spheres, , have played a major role in the study of the double suspension and have been used to get information about the homotopy groups of spheres and Moore spaces and to construct product decompositions of related spaces. In this paper we calculate for odd primes . When has the form , the result is well known, but these are exceptional cases in which the homology has polynomial growth. We find that in general the homology has exponential growth and in some cases also has higher -torsion. The calculations are applied to construct a -local product decomposition of for which demonstrates a mod homotopy exponent in these cases.

     

The functor A min on p-local spaces

In a previous paper, the authors gave the finest functorial decomposition of the loop suspension of a p-torsion suspension. The purpose of this paper is to generalize this theorem to the loop suspension of arbitrary p-local path connected spaces. The authors are grateful for support from National Sciences Engineering Research Council of Canada and National University of Singapore.