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M Goodman

Publications and source records attributed to M Goodman.

At least 55 records · Page 3Linked to original sources
PubMed1991

Topochemical analysis of morphiceptin and dermorphin bioactivities.

To elucidate the topochemical requirements for bioactivities of morphiceptin (Tyr-Pro-Phe-Pro-NH2) and dermorphin (Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2), we have designed and synthesized two diastereomers Tyr-(L and D)-(NMe)Ala-Phe-D-Pro-NH2. Both the analogs display high activities in the guinea pig ileum assay. The only difference in the composition of these two diastereomers arises from the chirality at residue 2. The high mu-receptor activities are attributed to structures where the Tyr1-L-(NMe)Ala2 amide bond assumes a cis configuration while the Tyr1-D-(NMe)Ala2 amide bond assumes a trans configuration. Accessible space studied for the second residues of these molecules confirms the fact that the L-(NMe)Ala2 analog belongs to the morphiceptin family of opioids while the D-(NMe)Ala2 analog belongs to the dermorphin class of opioids. The similarity in the spacial array of the analogs explains their high mu-receptor activities and indicates that they are likely recognized at the same opioid receptor.

Amino Acid Sequence↗
PubMed1991

Duplication of the gamma-globin gene mediated by L1 long interspersed repetitive elements in an early ancestor of simian primates.

Regions surrounding the single gamma-globin gene of galago and the duplicated gamma 1- and gamma 2-globin genes of gibbon, rhesus monkey, and spider monkey were sequenced and aligned with those from humans. Contrary to previous studies, spider monkey was found to have not one but two gamma-globin genes, only one of which (gamma 2) is functional. The reconstructed evolutionary history of the gamma-globin genes and their flanking sequences traces their origin to a tandem duplication of a DNA segment approximately 5.5 kilobases long that occurred before catarrhine primates (humans, apes, and Old World monkeys) diverged from platyrrhines (New World monkeys), much earlier than previously thought. This reconstructed molecular history also reveals that the duplication resulted from an unequal homologous crossover between two related L1 long interspersed repetitive elements, one upstream and one downstream of the single ancestral gamma-globin gene. Perhaps facilitated by the redundancy resulting from the duplication, the gamma-globin genes escaped the selective constraints of embryonically functioning genes and evolved into fetally functioning genes. This view is supported by the finding that a burst of nonsynonymous substitutions occurred in the gamma-globin genes while they became restructured for fetal expression in the common ancestor of platyrrhines and catarrhines.

Animals↗
PubMed1991

Concerted evolution led to high expression of a prosimian primate delta globin gene locus.

The delta globin gene in simian primates is either weakly expressed (in hominoids and New World monkeys) or silent (in Old World monkeys). In prosimian primates, however, an unequal homologous crossover between the psi eta and delta loci of lemurs produced a hybrid psi eta delta pseudogene locus, whereas in tarsier the delta locus encodes a beta-type chain found in 18% of adult tarsier hemoglobin molecules. In the present study, the nucleotide and amino acid sequences of the galago delta and beta globin genes and their encoded peptides were determined, and evidence is provided showing that the galago delta locus encodes a beta-type chain (beta 2) found in 40% of the galago fetal and postnatal hemoglobin molecules, whereas the beta locus encodes the remaining 60% of the beta-type chain (beta 1). Galago beta 1 and beta 2 chains differ from each other by only one amino acid residue. The homology between the galago delta and beta loci extends from 800 base pairs 5' of the proximal CCAAT element to near the end of exon 3 as a result of a recombination event in which beta sequence replaced delta sequence. After this initial recombination event, concerted evolution between the loci continued over their conserved coding, intron 1, and promoter regions but failed to occur between the two loci in their intron 2 and distal 5'-flanking sequences where the two loci have now diverged by 20%. Calculations based on this divergence value and on a rate of noncoding sequence evolution of 4.2 x 10(-9) to 5.5 x 10(-9) substitutions/site/year for the lorisiform lineage to galago yielded a date of 18-24 million years ago for the initial recombination event. The fact that the promoter sequences of the galago delta locus are the same as that of the galago beta locus may account for the high level of expression of the galago delta gene.

Amino Acid Sequence↗
PubMed1991

Conformational studies of stereoisomeric 14-membered cyclic enkephalin analogues containing 1-naphthylalanine at the fourth position: chirality effect of leucine at the fifth position on biological activity and receptor selectivity.

In order to study structure-activity relationships of enkephalin-related analogues, we report the biological activity and conformational analysis of four 14-membered cyclic enkephalin analogues with beta-(1-naphthyl) alanine in place of phenylalanine at the fourth position, Tyr-c[D-A2bu-Gly-(L and D)-beta Nal(1)-(L and D)-Leu]. The L-beta Nal(1)-containing analogues display higher activity at both the mu and delta receptors than the corresponding analogues with the L-Phe residue. In contrast to the linear enkephalins, the cyclic analogues with the D-beta Nal(1) residue are also active at the mu receptor since the relative spatial arrangement of functional groups required for biological activity is achieved by the constrained nature of the cyclic molecules. A comparison of the findings from the conformational analysis and biological assays establishes that relatively extended structures, in which the two aromatic side chains are oriented in opposite directions with a approximately 14 A separation, is required for activity at the mu receptor. On the other hand, folded conformations with nearly parallel orientations and a close proximity (less than 10A) of the aromatic rings of the Tyr and beta Nal(1) residues are required for activity at the delta receptor. It should be noted that the overall structures and thus the biological profiles of the 14-membered cyclic enkephalin analogues are strongly dependent on the conformation of the second residue. The folded conformations with parallel orientation of the two aromatic side chains of Tyr-c[D-A2bu-Gly-L-beta Nal(1)-D-Leu] is stabilized by an interaction between the Tyr phenolic OH proton and beta Nal(1) C*O groups. This analogue, which shows the highest activity at both the mu and delta receptors among the four stereoisomers studied, displays an increase of the fraction of the side-chain chi 1 = t conformer for the beta Nal(1) residue. It is concluded that the incorporation of the D-Leu residue at the fifth position increases the relative fraction of the folded conformations with parallel orientation of the aromatic side chains, and hence enhances activity at the delta receptor as compared to the corresponding L-Leu containing analogue.

Alanine↗
PubMed1991

Cyclic retro-inverso dipeptides with two aromatic side chains. I. Synthesis.

A series of cyclic retro-inverso dipeptides--2-[(4-hydroxy)benzyl]-5-benzyl-4,6(1H,2H,3H,5H)-pyrimidinedi one (c[mPhe-gTyr]), 2-benzyl-5-[(4-hydroxy)benzyl]-4,6(1H,2H,3H,5H)-pyrimidinedione (c[mTyr-gPhe]), and 2-benzyl-5-amino-5-[(4-hydroxy)benzyl]-4,6(1H,2H,3H,5H)-pyrimidinedione (c[(alpha-amino)mTyr-gPhe])--were synthesized in order to define the minimum structural requirements for binding affinity with opiate receptors and biological activity. Although the first two compounds lack a free amine proposed to be necessary for receptor recognition, the c[mPhe-gTyr] and c[mTyr-gPhe] analogues serve as model molecules in conformational studies of the target analogue, c[(alpha-amino)mTyr-gPhe]. The cis- and trans-c[(alpha-amino)mTyr-gPhe] contain all the functional groups such as the amine and phenolic groups in the tyrosine, and the aromatic group in the phenylalanine, necessary for opiate activity. In addition, the c[(alpha-amino)mTyr-gPhe] analogues possess similar geometries to the Tyr-Pro part of morphiceptin (Tyr-Pro-Phe-Pro-NH2) whose high mu-receptor activity is attributed to conformations with the Tyr-Pro amide bond in a cis conformation because the peptide bonds assume a cis conformation. However, both analogues are inactive in the guinea pig ileum and the mouse vas deferens assays. This may result from wrong orientation of the benzyl group of the gPhe residue with respect to the (alpha-amino)mTyr residue. Conformational studies of these molecules using 1H-nmr spectroscopy and molecular mechanics calculations will be reported in the following paper. Results of conformational analysis should provide information about backbone-side-chain interactions in the retro-inverso peptide chains since all the fundamental structural elements of the retro-inverso peptides are included in these model systems even though the peptide bonds must assume a cis conformation.

Amino Acid Sequence↗
PubMed1991

Cyclic retro-inverso dipeptides with two aromatic side chains. II. Conformational analysis.

The conformations of cis and trans cyclic retro-inverso dipeptides--2-[(4-hydroxy)benzyl]-5-benzyl-4,6(1H,2H,3H,5H)-pyrimidinedi one (c[mTyr-gPhe]), and 2-benzyl-5-amino-5-[(4-hydroxy)benzyl]-4,6(1H,2H,3H,5H)-pyrimidinedione (c[mTyr-gPhe]), and 2-benzyl-5-amino-5-[(4-hydroxy)benzyl]-4,6(1H,2H,3H,5H)-pyrimidinedione (c[(alpha-amino)mTyr-gPhe])--and the parent cyclic dipeptides--c[tyrosyl-phenylalanine] (cis-c[L-Tyr-L-Phe]) and c[tyrosyl-D-phenylalanine] (trans-c[L-Tyr-D-Phe])--were studied by using 1H-nmr spectroscopy and semiempirical energy calculations. In the cis compounds of all the cyclic retro-inverso and parent dipeptides, the most stable conformer has both aromatic side chains sharing the space over the backbone ring in a "face-to-face" fashion. All the trans compounds predominantly assume a "sandwich" conformation in which the two aromatic rings are folded back over the backbone ring on opposite sides. However, different conformational preferences were observed for the backbones between the retro-inverso and parent cyclic dipeptides. The parent cyclic dipeptide trans-c[L-Tyr-D-Phe] adopts two types of boat structures with different side-chain orientations in almost equal amounts: one with the Tyr side chain in a pseudoaxial position and the Phe side chain in a pseudoequatorial position, the other with the Tyr side chain in a pseudoequatorial position and the Phe side chain in a pseudoaxial position. On the other hand, the cyclic retro-inverso dipeptides trans-c[mPhe-gTyr] and trans c[mTyr-gPhe] assume only one type of boat structure in which the malonyl side chain is in a pseudoequatorial and the gem-diamino side chain is in a pseudoaxial position. In addition to the preferred conformations, the conformational energies of the C alpha--C beta bonds in the malonyl and gem-diamino residues were estimated from the temperature variation of vicinal 1H--1H coupling constants for the H--C alpha--C beta--H groupings observed for the trans isomers of cyclic retro-inverso dipeptides. The energies were evaluated to be 1.1 and 1.8 kcal mol-1 for the malonyl and gem-diamino residues, respectively. Applying these energies to the parent cyclic dipeptide trans-c[L-Tyr-D-Phe], the observed fractions of three side-chain conformations are reasonably reproduced. The conformational energies as well as conformational properties of the molecules estimated in this investigation may be useful to refine force constants for both parent and retro-inverso peptides with aromatic side chains.

Amino Acid Sequence↗
PubMed1991

Absolute configuration for peptidomimetic residues in bioactive peptides.

A modern method is reported for the assignment of absolute configuration for peptidomimetics in bioactive peptides by use of 1H-NMR parameters in solution. Four peptide systems incorporating either retro-inverso modifications or 2-aminocyclopentanecarboxylic acid (2-Ac5c) as a peptidomimetic for proline are discussed. (1) Two 14-membered cyclic dermorphin analogs Tyr-c[D-A2bu-Phe-gPhe-(S and R)-mLeu] with a reverse amide bond between gPhe and mLeu residues where gPhe denotes a gem-diamino analog of Phe and mLeu refers to a malonyl analog of Leu. (2) Two cyclic hexapeptides related to somatostatin, c[gSar6-(S and R)-mPhe7-D-Trp8-Lys9-Thr10-Phe11], with a reverse amide bond between the gSar and mPhe residues where the gSar and mPhe denote the gemdiamino and malonyl analogs of the Sar and Phe residues, respectively. The superscript numbers refer to positions in native somatostatin. (3) Cyclic hexapeptide somatostatin analogs containing 2-Ac5c [trans-(1S,2S)-2-Ac5c, trans-(1R,2R)-2-Ac5c,cis-(1R,2S)-2-Ac5c, and cis-(1S,2R)-2-Ac5c] in place of proline c[(2-Ac5c)6-Phe7-D-Trp8-Lys9-Thr10-Phe11]. (4) Morphiceptin related analogs incorporating a cis-2-Ac5c residue as shown in Tyr-cis-2-Ac5c-Phe-Val-NH2. The methodology described in this investigation could be applied to a wide variety of peptide systems.

Magnetic Resonance Spectroscopy↗
PubMed1991

Social policy on the use of aversive interventions: empirical, ethical, and legal considerations.

In an effort to address the controversy regarding the use of aversive interventions in the treatment of individuals with developmental disabilities, this paper presents a review of the literature on the efficacy of such interventions, along with brief reviews of the ethical and legal issues involved. In general, there appears to be empirical, ethical, and legal support for the continued availability of aversive interventions as treatment options, but only if sufficient safeguards are in place.

Autistic Disorder↗
PubMed1991

The utility of 2-hydroxypropyl-beta-cyclodextrin as a vehicle for the intracerebral and intrathecal administration of drugs.

The substituted glucopyranose ring structure 2-hydroxypropyl-beta-cyclodextrin (CDEX) increases the solubility of molecules by inclusion of the agent in the lipophilic interior of the ring. This property is of particular use for the administration of molecules by the intracerebral (ICV) or intrathecal (IT) routes. In concentrations up to 40% w/v (isotonic), this agent (10 microliters) effect upon nociceptive or motor function after IT injection or on EEG and general behavior after ICV injection in rats. Using 20% CDEX, there is no change in the ED50 as compared to saline on the hot plate (HP) after IT injection of morphine, D-Ala2-D-Leu5 enkephalin or Tyr-Aib-Gly-gPhe-mAib-NH2, (Aib: alpha-aminoisobutyric acid) although there is an increase in their respective durations of effect. Cyclic peptide opioids: Tyr-c[D-A2bu-Gly-D-beta Nal(1)-D-Leu] (A2bu: alpha, gamma-diaminobutyric acid; beta-Nal(1): beta-naphthylalanine(1)) or Tyr-c[DA2bu-Gly-beta Nal(1)-D-Leu] are insoluble in saline but are readily dissolved in CDEX, and display a naloxone-sensitive antinociception following spinal administration. In other studies, saline insoluble capsaicin is administered in 25% dimethylsulfoxide (DMSO) or 20% CDEX (15 microliters; 5 mg/ml) which result in a significant reduction in the spinal levels of substance P and calcitonin gene related peptide and an increase in the HP latency. DMSO alone, but not CDEX alone, reduces the levels of the two peptides. These data emphasize the utility of complexation with CDEX for intracerebral drug delivery and compatibility with brain and spinal tissue.

2-Hydroxypropyl-beta-cyclodextrin↗
PubMed1991

Photon irradiation of unresectable carcinomas of salivary glands.

This paper presents our experience and the local control rates of a group of patients with inoperable and unresectable lesions treated by photon irradiation from 1980 through 1989. The patient material consists of a total of 24 patients, 9 with carcinoma arising from the parotid gland and 15 with lesions in the minor salivary glands, mainly the oral cavity and oropharynx. The pathologic slides were reviewed and malignancy of various cell types confirmed. The 5-year actuarial local control of parotid gland lesions after photon irradiation was 100% and the survival rate was 65%. For the minor salivary gland lesions, the 5-year actuarial local control was 78% and the survival rate with or without disease was 93%. All lesions were irradiated by accelerated hyperfractionated photons (bid) with 1.6 Gy per fraction, intermixed with various boost techniques including electron beam, intraoral cone, interstitial implant, and/or submental photons for a total of 65-70 Gy. Most treatment failures of parotid cancer were due to distant metastases. The present series showed excellent local control and satisfactory survival of inoperable and unresectable salivary gland carcinomas after state-of-the-art photon irradiation, comparable to that achieved by neutron irradiation. The late complications were minimal. A controlled randomized trial may be indicated.

Adenocarcinoma↗
PubMed1991

Adjuvant systemic therapy of stage I and II breast cancer.

The value of adjuvant systemic therapy has been clearly demonstrated in both node-positive and node-negative patients. However, there are many women with favorable prognoses whose breast cancer recurs. It has been possible only recently to identify subsets of patients who are at definite risk for recurrence. Advances both in selection and treatment of patients with early-stage breast cancer are being made as critical research questions are delineated and examined in prospective randomized trials.

Breast Neoplasms↗
PubMed1991

Phylogenetic scanning: a computer-assisted algorithm for mapping gene conversions and other recombinational events.

An algorithm, 'phylogenetic scanning', is described for mapping gene conversion events where comparative DNA sequence data are available from different species. In this algorithm, sets of hypothetical phylogenetic trees are constructed that describe possible sequence relationships due to gene conversions in different species lineages; these trees are then evaluated by the principle of parsimony at intervals in the sequence alignment. When used to map gene conversion events that occurred between the pair of gamma-globin genes of higher primates, the algorithm gives results nearly identical to those obtained using a tedious manual approach. Suggestions are also provided for adaptation of this procedure to the analysis of other recombination events.

Algorithms↗
PubMed1991

Key relationships of never married, childless older women: a cultural analysis.

The key relationships of never married, childless older women, that is, those relationships described as central, compelling, enduring, or significant throughout their lifetimes, were explored in this study. Analysis of qualitative, ethnographically based interviews with 31 women indicated that the key relationships they describe fall into three classes: ties through blood, friendships, and those we label "constructed" ties (kin-like nonkin relations). We report on types of key interpersonal relationships of these women and also examine limits to these key relations, describing some strategies these women have adopted for gaining kin-like relations and the problems inherent in them for the expectation of care in later life. Theoretical work by anthropologist David Schneider concerning American kinship as a cultural system is used to explore dimensions of these relationships.

Achievement↗
PubMed1991

Cultural differences among elderly women in coping with the death of an adult child.

This article describes differences between elderly Jewish and non-Jewish women in dealing with the death of an adult child. Dimensions of difference include the meaning of the death to the mother, her expression of grief, and her conceptualization of the future in the face of the loss. Results are based on data from 12 Jewish and 17 non-Jewish women taking part in a larger study examining generativity as a predictor of well-being in women over 60. Data collection included in-depth life histories and quantitative evaluations of well-being, affect, generativity, and personality variables associated with mothering. Qualitatively, Jewish women were depressed and fixed in grief, with the loss remaining central to their lives. Non-Jewish women articulated philosophies of acceptance, putting the death in a perspective that enabled them to move beyond their loss. Well-being, affect, generativity, and personality measures statistically supported the qualitative differences found between the groups.

Adaptation, Psychological↗
PubMed1991

Molecular evolution of the psi eta-globin gene locus: gibbon phylogeny and the hominoid slowdown.

An 8.4-kb genomic region spanning both the psi eta-globin gene locus and flanking DNA was sequenced from the common gibbon (Hylobates lar). In addition, sequencing of the entire orthologous region from galago (Galago crassicaudatus) was completed. The gibbon and galago sequences, along with published orthologous sequences from 10 other species, were aligned. These noncoding nucleotide sequences represented four human alleles, four apes (chimpanzee, gorilla, organgutan, and gibbon), an Old World monkey (rhesus monkey), two New World monkeys (spider and owl monkeys), tarsier, two strepsirhines (galago and lemur), and goat. Divergence and maximum parsimony analyses of the psi eta genomic region first groups humans and chimpanzees and then, at progressively more ancient branch points, successively joins gorillas, orangutans, gibbons, Old World monkeys, New World monkeys, tarsiers, and strepsirhines (the lemuriform-lorisiform branch of primates). This cladistic pattern supports the taxonomic grouping of all extant hominoids into family Hominidae, the division of Hominidae into subfamilies Hylobatinae (gibbons) and Homininae, the division of Homininae into tribes Pongini (orangutans) and Hominini, and the division of Hominini into subtribes Gorillina (gorillas) and Hominina (chimpanzees and humans). The additional gibbon and galago sequence data provide further support for the occurrence of a graded evolutionary-rate slowdown in the descent of simian primates, with the slowing rate being more pronounced in the great-ape and human lineages than in the gibbon or monkey lineages. A comparison of global versus local molecular clocks reveals that local clock predictions, when focused on a specific number of species within a narrow time frame, provide a more accurate estimate of divergence dates than do those of global clocks.

Animals↗
PubMed1991

Biological and conformational studies of [Val4]morphiceptin and [D-Val4]morphiceptin analogs incorporating cis-2-aminocyclopentane carboxylic acid as a peptidomimetic for proline.

We report the synthesis, biological activity, and conformational analysis of tetrapeptide analogs related to [Val4]morphiceptin and [D-Val4]morphiceptin in which the proline at the second position has been replaced with cis-2-aminocyclopentane carboxylic acid (cis-2-Ac5c). Since the cis-2-Ac5c residue contains a normal amide, only the trans form has been observed about the amide bond between the first and second residues. The cis-2-Ac5c is a beta amino acid with two chiral centers resulting in two possible configurational isomers, namely (1S, 2R) and 1R, 2S) forms. The analogs containing the (1S, 2R)-Ac5c residue show activity at the mu-receptor but are inactive at the delta-receptor, resulting in a high selectivity for the mu-receptor. The (1R,2S)-Ac5c containing analogs are completely inactive at both the mu- and delta-receptors. The conformational analysis indicates that the separation of the aromatic rings of the tyrosine and phenylalanine residues, as expressed by the center-to-center distance, is 10.1-12.7 A for the preferred conformations of the bioactive analogs containing the (1S,2R)-Ac5c residue while a range of 4.8-7.0 A is observed for the preferred conformations of the inactive analogs with the (IR,2S)-Ac5c residue. A comparison of the findings from the conformational analysis and biological assays establishes the fact that a relatively large separation of the two aromatic side chains is required for the mu-opioid receptor activity of these molecules. Since the tetrapeptide amides studied in this investigation show similar biological profiles to those of the morphiceptin-related analogs, we have compared the preferred conformations estimated for the cis-2-Ac5c containing analogs with those of morphiceptin. One of the low energy conformations calculated for morphiceptin with the cis form about the tyrosine and proline residues has considerable topological similarity with the bioactive analogs containing the (1S,2R)-Ac5c residue, indicating that the cis from about these two residues is required for the biological activity of the morphiceptin-related analogs containing the proline at the second position.

Amino Acid Sequence↗
PubMed1991

Solid phase synthesis of human growth hormone-releasing factor analogs containing a bicyclic beta-turn dipeptide.

Three analogs derived from the N-terminal 29-residue fragment of human growth hormone-releasing factor (hGRF) which contained a bicyclic beta-turn dipeptide (BTD) at 7-8, 8-9, and 9-10 positions were synthesized by solid phase methodology to ascertain if the beta-turns are important for the biological activity of hGRF and also to show the applicability of the BTD unit to solid phase synthesis. All three analogs were obtained in good yield and purity indicating that the BTD unit can be used in the usual condition of solid phase synthesis. The capacity of these analogs to release growth hormone (GH) was tested in an in vitro bioassay using rat anterior pituitary cells. All three BTD-containing analogs showed the same maximal GH secretion with parallel dose-response curves to that of hGRF(1-29)NH2, except their relative potencies were very low.

Amino Acid Sequence↗