RING domains of E3 ligases promote transfer of Ub (ubiquitin) from the E2~Ub conjugate to target proteins. In many cases interaction of the E2~Ub conjugate with the RING domain requires its prior dimerization. Using cross-linking experiments we show that E2 conjugated ubiquitin contacts the RING homodimer interface of the IAP (inhibitor of apoptosis) proteins, XIAP (X-linked IAP) and cIAP (cell...

A series of dATP and dCTP nucleotide analogs have been synthesized which are modified by attachment of aliphatic linkers containing a functional group to the amino-nitrogen at the hydrogen bonding positions of the bases, that is, at the 6-position of adenine and the 4-position of cytosine. These nucleotides are incorporated into DNA probes by standard nick-translation protocols. DNA probes labe...

The various soluble liver protein-carcinogen conjugates produced in vivo by two hepatocarcinogens have been resolved and analyzed according to molecular size. In addition, the molecular sizes of the principal soluble conjugates of three types of carcinogens have been compared in order to deduce whether they originate from a common or similar target pro tein. Adult male rats were fed the liver c...

A polyelectrolyte complex micelle (PECM)-based delivery system for targeting folate (FOL) receptor overexpressing tumor cells is demonstrated using poly(ethylene glycol) (PEG)-conjugated oligonucleotide (ODN). The tumor targeting property was conferred to the PECM by tethering a folate moiety to the distal end of the PEG segment in an anti-sense green fluorescent protein (GFP) ODN-PEG conjugate...

Anthracycline, either daunomycin or doxorubicin, was site specifically attached to the carbohydrate moiety of a monoclonal anticarcinoembryonic antigen antibody by using amino-dextran as the intermediate carrier. The reaction resulted in an immunoconjugate that contains approximately 20 to 25 molecules of drug per molecule of immunoglobulin G. Flow-cytometric studies revealed the retention of t...

Peroxidic antimalarial agents including the sequiterpene artemisinins and the synthetic 1,2,4-trioxolanes function via initial intraparasitic reduction of an endoperoxide bond. By chemically coupling this reduction to release of a tethered drug species it is possible to confer two distinct pharmacological effects in a parasite-selective fashion, both in vitro and in vivo. Here we demonstrate th...

To explore the role of the T3, T4, and LFA-1 molecules in high and low "avidity" interactions between SB2-specific cytotoxic T lymphocyte (CTL) clones and their targets, monoclonal antibody-mediated inhibition of cytotoxicity has been studied in experiments that vary the "avidity" of interaction in three different ways. 1) Previous results have been extended with respect to different CTL clones...

We propose and study kernel conjugate gradient methods (KCGM) with random projections for least-squares regression over a separable Hilbert space. Considering two types of generated by randomized sketches Nyström subsampling, we prove optimal statistical results respect to variants norms the algorithms under suitable stopping rule. Particularly, our show that if projection dimension is proporti...

In this paper, we present new variants of global bi-conjugate gradient (Gl-BiCG) and global bi-conjugate residual (Gl-BiCR) methods for solving nonsymmetric linear systems with multiple right-hand sides. These methods are based on global oblique projections of the initial residual onto a matrix Krylov subspace. It is shown that these new algorithms converge faster and more smoothly than the Gl-...