Robert Scott Root-Bernstein

Amino acid pairing

Abstract A set of amino acid pairings are presented which may allow protein-to-protein information transfers. Amino acid pairing is only possible on a parallel β ribbon and involves both the polypeptide backbones and the side chains. Model building revealed that of the 210 possible amino acid pairs of the standard 20 amino acids, no more than 26 could be built to meet standard criteria for bonding. Of these 26, 14 were found to be genetically encoded when the codons are read as if they paired in a parallel manner (i.e. in a manner reflecting the structural parallelism of the amino acid pairings); the other 12 pairings were derivatives of the coded pairings in which a single base of the codon triplet had been varied in accordance with Cricks (1966) “wobble hypothesis.” Evidence for the pairings is presented from colligative studies of polyamino acids. Ways of testing the hypothesis further are suggested. Its implications for the Central Dogma and theories of the origin of life are discussed.

Serotonin binding sites I. structures of sites on myelin basic protein, LHRH, MSH, ACTH, interferon, serum albumin, ovalbumin and red pigment concentrating hormone

We report the results of nuclear magnetic resonance spectroscopy studies of combinations of serotonin (5-hydroxytryptamine) with the tryptophan peptide sequence and similar peptides from myelin basic protein. The binding site appears to consist of the sequence Arg Phe Ser Trp. Similar serotonin binding sites were found to exist on LHRH (Tyr Ser Trp) and MSH-ACTH tetrapeptide (Phe Arg Trp). These binding sites are specific to serotonin as is demonstrated by lack of binding by dopamine, histamine, acetylcholine and a dozen other pharmacologically active amines and indoles. Drugs known to affect serotonin levels, e.g., fenfluramine and L-DOPA, bind weakly to these sites. Structural and functional similarities between the tryptophan peptide, LHRH, and MSH-ACTH with an ACTH-like peptide of human leukocyte interferon, with human and bovine serum albumin, hen ovalbumin, and with red pigment concentrating hormone suggest that the latter peptides may also contain similar serotonin binding sites. The elucidation of serotonin binding sites on these peptides and proteins has implications for understanding various aspects of cancer, autoimmunity, neurological disease, and peptide hormone control.

An explanation of prevention and suppression of experimental allergic encephalomyelitis

An explanation of experimental allergic encephalomyelitis prevention and suppression is presented based upon evidence that the active unit in disease induction is an encephalitogen-adjuvant complex. The stereochemical complementarity in structure of the encephalitogen and adjuvant is mirrored in complementarity in the recognition sites of lymphocyte populations activated against encephalitogen and adjuvant. Since two complementary lymphocyte populations are necessary for disease induction, any procedure that prevents the development of one of these populations will prevent disease induction. Any procedure that eliminates one population after induction has occurred will suppress the disease. We argue that all extant data support the hypothesis. Several new experiments are proposed to further test it.

‘Molecular sandwiches’ as a basis for structural and functional similarities of interferons, MSH, ACTH, LHRH, myelin basic protein, and albumins

Sequential similarities between the tryptohan peptide of myelin basic protein (residues 111–121), luteinizing hormone releasing hormone, melanotropin, adrenocorticotropin (residues 1–13), human leukocyte interferon (residues 28–40), and various segments of human and bovine serum albumin and hen ovalbumin are presented. It is suggested that these structural similarities may explain observations concerning common functional characteristics such as serotonin modulation, immunological activity with the adjuvant muramyl dipeptide, immunological cross‐reactivity, and the possible MSH‐ACTH‐like activity of a pepsin‐derived peptide of interferon.

Protein replication by amino acid pairing

Biological problems concerning the origin of life and the mode of prion replication (Prusiner, 1982) may require protein replication (the synthesis of one protein sequence from another) as part of their solution. It is suggested that complementarity between protein sequences may be determined by amino acid pairing (Root-Bernstein, 1982a). Two mechanisms using the complementarity afforded by amino acid pairing are proposed. Experimental tests of the mechanisms are suggested.

Fenfluramine binds 5-hydroxytryptophan.

Fenfluramine, an anorexigenic drug, lowers serotonin (5-hydroxytryptamine) and 5-hydroxyindoleacetic acid levels in brain, spinal fluid, and blood, and has been used as a treatment for autism. Fenfluramines mode of action is unknown. We present evidence from chromatography and nuclear magnetic resonance spectroscopy that fenfluramine selectively binds the serotonin and 5-hydroxyindoleacetic acid precursor, 5-hydroxytryptophan. The mode of binding may have general applications for the understanding of drug activity, receptor binding, and for the design of specific antagonists to aromatic compounds.

Spanish toxic-allergic syndrome: an explanation.

Although in Aberdeen the first pre-pregnancy clinic was started in 1972, the above approach was only adopted for the Grampian area in January, 1982. At present there is a pre-pregnancy diabetic, genetic, and renal consultant service and a general referral consultant pre-pregnancy clinic. The last may prove to be unnecessary as it remains the policy for those women with a history of reproductive failure to have continued care from the obstetrician to whom they were known during the previous obstetric events and their pre-pregnancy care stems from the postnatal clinic attendance. However, there may remain a need for a hospital based general prepregnancy clinic for referral of certain nulliparous women with particular problems, but it is too early to assess this in Grampian as we are still receiving differing responses to the newsletter circulated to all general practitioners in the area announcing this programme. There is family planning and planning a family. Both merit an equally energetic and structured approach no matter how limited are the resources.

The problem of problems

Abstract Problems of generating and evaluating problems are discussed and the subjective nature of these processes highlighted. Criteria for problem evaluation are presented as a means to minimize this subjectivity. Areas of continuing ignorance concerning problem generation and evaluation are defined and suggestions made for investigating them.

Selective chirility and the origins of life

Abstract Despite 120 years of research into the origins of chirility, the problem of how one enantiomer was selected over its chiral pair for use in the origins of life is still unsolved. I suggest that no solution has been found because the assumptions implicit in the problem statement are invalid. An alternative description of the problem is given and demonstrated to be capable of resolution. Two possible resolutions are sketched. Methods and criteria are stated for testing and evaluating the problem statement and its possible solutions.